1
|
Venkatesh SB, Shetty SS. Role of genetic polymorphisms in residual ridge resorption of mandible - A scoping review. JAPANESE DENTAL SCIENCE REVIEW 2025; 61:22-30. [PMID: 40125334 PMCID: PMC11927421 DOI: 10.1016/j.jdsr.2025.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Revised: 01/20/2025] [Accepted: 02/20/2025] [Indexed: 03/25/2025] Open
Abstract
Residual ridge (RR) refers to the clinical alveolar ridge that remains after the bone and soft tissues have healed following tooth extraction. This ridge undergoes resorption, which is most rapid during the first six months of post-extraction. Subsequently, bone resorption continues at a slower pace throughout life, leading to significant loss of jaw structure over time. This process is commonly known as residual ridge resorption (RRR). RRR is a major factor contributing to the loss of stability and retention, especially in mandibular complete dentures. Severe resorption of the maxillary and mandibular ridges can also lead to a sunken cheek appearance, poorly fitting and unstable dentures, and associated pain and discomfort. Though the etiology of residual ridge resorption remains unclear. It is believed that certain cytokines and individual genetic variations may influence the RRR process. Thus, reviewing the studies that discuss genetic association with the health and resorption of alveolar bone may give clear view on the etiology, help to define the risk and strategize preventive and personalized management of the disease. Hence, we undertook a scoping review to understand the potential genetic factors influencing the Residual ridge resorption (RRR). This review employed PRISMA-ScR extension protocols for scoping review. The results of the study provided significant association between genetic polymorphisms, especially of single gene nucleotide polymorphisms with mandibular residual ridge resorption. Hence understanding the genetic predisposition of patients can guide the clinicians in identifying patients at higher risk of RRR, enabling preventive measures, proactive intervention and careful designing of the prothesis.
Collapse
Affiliation(s)
- Swapna B. Venkatesh
- Department of Prosthodontics and Crown & Bridge, Manipal College of Dental Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka 576104, India
| | - Smitha Sammith Shetty
- Department of Oral Pathology and Microbiology, Manipal College of Dental Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka 576104, India
| |
Collapse
|
2
|
Liang L, Dong Z, Shen Z, Zang Y, Yang W, Wu L, Bao L. Inhibitory effects of umbelliferone on carbon tetrachloride-induced hepatic fibrosis in rats through the TGF‑β1‑Smad signaling pathway. Mol Med Rep 2025; 32:171. [PMID: 40242963 PMCID: PMC12020354 DOI: 10.3892/mmr.2025.13536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Accepted: 03/19/2025] [Indexed: 04/18/2025] Open
Abstract
Hepatic fibrosis (HF) is a critical marker of advanced‑stage chronic liver disease and involves pivotal contributions from hepatic stellate cells (HSCs). Currently, there are no effective treatments for HF. Umbelliferone (7‑hydroxycoumarin; UMB) is a natural compound with significant anti‑inflammatory, antioxidant and anti‑tumor activities. However, its potential efficacy in treating HF has not been studied. The present study explored the protective effects of UMB against HF, targeting the TGF‑β1‑Smad signaling pathway to explore the underlying mechanisms of UMB. Carbon tetrachloride (CCl4) was injected intraperitoneally to induce HF in rats and primary HSCs were treated in vitro with UMB to investigate the improvement effect of UMB on HF. The levels of fibrosis markers, inflammation, oxidative stress and TGF‑β1‑Smad signaling pathway in the rat liver tissue and HSCs were detected using hematoxylin and eosin staining, enzyme‑linked immunosorbent assay, reverse transcription‑quantitative PCR, Cell Counting Kit‑8 and western blotting. The improvement in liver histopathology, liver function indexes and fibrosis markers demonstrated that UMB markedly inhibited the CCl4‑induced HF and inflammation in the rats. Additionally, UMB prominently reduced the pro‑inflammatory factors and oxidative stress levels. In vitro, UMB markedly inhibited primary HSC activation and decreased alpha‑smooth muscle actin and collagen I expression. The mechanism experiment proved that UMB inhibited the TGF‑β1‑Smad signaling pathway and ameliorated HF. The present study was the first to demonstrate, to the best of the authors' knowledge, that UMB might be a promising natural active compound for treating HF. Its therapeutic effect is associated with its modulation of the TGF‑β1‑Smad signaling pathway.
Collapse
Affiliation(s)
- Lijuan Liang
- College of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010110, P.R. China
| | - Zhiheng Dong
- Department of Pharmacy, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010030, P.R. China
| | - Ziqing Shen
- College of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010110, P.R. China
| | - Yifan Zang
- College of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010110, P.R. China
| | - Wenlong Yang
- College of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010110, P.R. China
| | - Lan Wu
- Mongolia Medical School, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010110, P.R. China
| | - Lidao Bao
- Department of Pharmacy, Hohhot First Hospital, Hohhot, Inner Mongolia Autonomous Region 010030, P.R. China
| |
Collapse
|
3
|
Sharma A, Balde A, Nazeer RA. A review on animal venom-based matrix metalloproteinase modulators and their therapeutic implications. Int Immunopharmacol 2025; 157:114703. [PMID: 40300352 DOI: 10.1016/j.intimp.2025.114703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Revised: 04/03/2025] [Accepted: 04/19/2025] [Indexed: 05/01/2025]
Abstract
Matrix Metalloproteinases (MMPs) belong to a family of proteolytic enzymes that degrade extracellular matrix components, such as collagen, elastin, laminin, and fibronectin. They also play a part in tissue remodeling by cleaving and rejoining the tissue proteins. Cancer, neurodegenerative disorders, cardiovascular diseases, arthritis, and chronic inflammatory conditions are just some of the diseases that can start or get worse when different MMPs are not working properly. Venomous Animals such as honeybees, toads, snakes, spiders, scorpions, jellyfish, and sea anemones contain venom-secreting glands, which help them defend against predators and immobilize their prey. The molecules that come from animal venom are a complicated mix of bioactive molecules, such as peptides, enzymes, proteins, and small organic compounds that do a number of biological things. Venom-derived molecules have been found to modulate MMP. These venoms and their components target specific signaling pathways, modifying MMP expression levels to either induce inflammation or exhibit anti-inflammatory effects. In this review, we study and explore different MMPs, such as MMP1, MMP2, MMP3, MMP7, MMP8, and MMP9, and their roles in the progression of certain diseases. We also look at different types of molecules derived from marine and land animal venom that are used as MMP modulators. We look at how they work by targeting specific signaling pathways to change MMPs and how they might be used as a medicine to stop diseases by decreasing MMPs.
Collapse
Affiliation(s)
- Ansumaan Sharma
- Biopharmaceuticals Lab, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, Tamil Nadu, India
| | - Akshad Balde
- Biopharmaceuticals Lab, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, Tamil Nadu, India
| | - Rasool Abdul Nazeer
- Biopharmaceuticals Lab, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, Tamil Nadu, India.
| |
Collapse
|
4
|
Turan B, Onem Ozbilen E, Tacal Aslan B, Yilmaz OO. Investigation of MMP1 rs1799750 and TGF-ß1 rs1800470 polymorphisms in individuals with different vertical facial patterns and temporomandibular joint disorder. Angle Orthod 2025; 95:317-322. [PMID: 39933558 PMCID: PMC12017557 DOI: 10.2319/070324-528.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 01/07/2025] [Indexed: 02/13/2025] Open
Abstract
OBJECTIVES To evaluate the effects of rs1799750 1G/2G polymorphism of the MMP1 gene and rs1800470 T/C polymorphism of the TGF-ß1 gene on temporomandibular disk displacement and vertical facial development. MATERIALS AND METHODS Sixty-six individuals were examined radiographically prior to evaluation of the signs/symptoms of temporomandibular disorders according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Class II, hyperdivergent individuals with TMD (+) were assigned to Group 1, and individuals with TMD (-) were included in Group 2; while Class I, normodivergent individuals with TMD (-) were included in Group 3. For genetic analysis, oral mucosa swab samples were collected, and genotype analysis was performed. RESULTS The incidence of 2G alleles in Group 2 (72.7%) was significantly higher than the other groups (P < .05). ANB angle and mean Wits of the 1G/1G genotype of the MMP1 gene were significantly lower than 1G/2G and 2G/2G. Mean Go-Gn of the 1G/1G genotype was significantly higher than that of 1G/2G. The mean SNB of the TGF-β1 TT genotype was significantly higher than TC. The mean Co-Gn of TT was significantly higher than CC. CONCLUSIONS A relationship was found between the 2G allele of rs1799750 1G/2G polymorphisms of the MMP1 gene and the risk of individuals developing disk displacement. Also, it was found that TGF-ß1 gene rs1800470 29 T/C polymorphisms had a detrimental effect on mandibular development.
Collapse
Affiliation(s)
- Begum Turan
- Corresponding author: Dr Begum Turan, Marmara Universitesi Basibuyuk Saglik Yerleskesi, Dis Hekimligi Fakultesi, Ortodonti Anabilim Dali, Maltepe 9/34854, Istanbul, Turkey (e-mail: )
| | | | | | | |
Collapse
|
5
|
Pomella S, Melaiu O, Dri M, Martelli M, Gargari M, Barillari G. Effects of Angiogenic Factors on the Epithelial-to-Mesenchymal Transition and Their Impact on the Onset and Progression of Oral Squamous Cell Carcinoma: An Overview. Cells 2024; 13:1294. [PMID: 39120324 PMCID: PMC11311310 DOI: 10.3390/cells13151294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Revised: 07/26/2024] [Accepted: 07/29/2024] [Indexed: 08/10/2024] Open
Abstract
High levels of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-2 and angiopoietin (ANG)-2 are found in tissues from oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). As might be expected, VEGF, FGF-2, and ANG-2 overexpression parallels the development of new blood and lymphatic vessels that nourish the growing OPMDs or OSCCs and provide the latter with metastatic routes. Notably, VEGF, FGF-2, and ANG-2 are also linked to the epithelial-to-mesenchymal transition (EMT), a trans-differentiation process that respectively promotes or exasperates the invasiveness of normal and neoplastic oral epithelial cells. Here, we have summarized published work regarding the impact that the interplay among VEGF, FGF-2, ANG-2, vessel generation, and EMT has on oral carcinogenesis. Results from the reviewed studies indicate that VEGF, FGF-2, and ANG-2 spark either protein kinase B (AKT) or mitogen-activated protein kinases (MAPK), two signaling pathways that can promote both EMT and new vessels' formation in OPMDs and OSCCs. Since EMT and vessel generation are key to the onset and progression of OSCC, as well as to its radio- and chemo-resistance, these data encourage including AKT or MAPK inhibitors and/or antiangiogenic drugs in the treatment of this malignancy.
Collapse
Affiliation(s)
- Silvia Pomella
- Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier, 00133 Rome, Italy; (S.P.); (O.M.); (M.M.); (M.G.)
| | - Ombretta Melaiu
- Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier, 00133 Rome, Italy; (S.P.); (O.M.); (M.M.); (M.G.)
| | - Maria Dri
- Department of Surgical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy;
| | - Mirko Martelli
- Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier, 00133 Rome, Italy; (S.P.); (O.M.); (M.M.); (M.G.)
| | - Marco Gargari
- Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier, 00133 Rome, Italy; (S.P.); (O.M.); (M.M.); (M.G.)
| | - Giovanni Barillari
- Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier, 00133 Rome, Italy; (S.P.); (O.M.); (M.M.); (M.G.)
| |
Collapse
|
6
|
Micek HM, Yang N, Dutta M, Rosenstock L, Ma Y, Hielsberg C, McCord M, Notbohm J, McGregor S, Kreeger PK. The role of Piezo1 mechanotransduction in high-grade serous ovarian cancer: Insights from an in vitro model of collective detachment. SCIENCE ADVANCES 2024; 10:eadl4463. [PMID: 38669327 PMCID: PMC11051664 DOI: 10.1126/sciadv.adl4463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 03/22/2024] [Indexed: 04/28/2024]
Abstract
Slowing peritoneal spread in high-grade serous ovarian cancer (HGSOC) would improve patient prognosis and quality of life. HGSOC spreads when single cells and spheroids detach, float through the peritoneal fluid and take over new sites, with spheroids thought to be more aggressive than single cells. Using our in vitro model of spheroid collective detachment, we determine that increased substrate stiffness led to the detachment of more spheroids. We identified a mechanism where Piezo1 activity increased MMP-1/MMP-10, decreased collagen I and fibronectin, and increased spheroid detachment. Piezo1 expression was confirmed in omental masses from patients with stage III/IV HGSOC. Using OV90 and CRISPR-modified PIEZO1-/- OV90 in a mouse xenograft model, we determined that while both genotypes efficiently took over the omentum, loss of Piezo1 significantly decreased ascitic volume, tumor spheroids in the ascites, and the number of macroscopic tumors in the mesentery. These results support that slowing collective detachment may benefit patients and identify Piezo1 as a potential therapeutic target.
Collapse
Affiliation(s)
- Hannah M. Micek
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA
| | - Ning Yang
- Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA
| | - Mayuri Dutta
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA
| | - Lauren Rosenstock
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA
| | - Yicheng Ma
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA
| | - Caitlin Hielsberg
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA
| | - Molly McCord
- Department of Mechanical Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA
- Biophysics Program, University of Wisconsin-Madison, Madison, WI 53705, USA
| | - Jacob Notbohm
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA
- Department of Mechanical Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA
- Biophysics Program, University of Wisconsin-Madison, Madison, WI 53705, USA
- University of Wisconsin Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA
| | - Stephanie McGregor
- Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA
- University of Wisconsin Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA
| | - Pamela K. Kreeger
- Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA
- Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA
- University of Wisconsin Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA
| |
Collapse
|
7
|
Varghese A, Waheed SO, Gorantla K, DiCastri I, LaRouche C, Kaski B, Fields GB, Karabencheva-Christova TG. Catalytic Mechanism of Collagen Hydrolysis by Zinc(II)-Dependent Matrix Metalloproteinase-1. J Phys Chem B 2023; 127:9697-9709. [PMID: 37931179 PMCID: PMC10659029 DOI: 10.1021/acs.jpcb.3c04293] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 10/16/2023] [Accepted: 10/18/2023] [Indexed: 11/08/2023]
Abstract
Human matrix metalloproteinase-1 (MMP-1) is a zinc(II)-dependent enzyme that catalyzes collagenolysis. Despite the availability of extensive experimental data, the mechanism of MMP-1-catalyzed collagenolysis remains poorly understood due to the lack of experimental structure of a catalytically productive enzyme-substrate complex of MMP-1. In this study, we apply molecular dynamics and combined quantum mechanics/molecular mechanics to reveal the reaction mechanism of MMP-1 based on a computationally modeled structure of the catalytically competent complex of MMP-1 that contains a large triple-helical peptide substrate. Our proposed mechanism involves the participation of an auxiliary (second) water molecule (wat2) in addition to the zinc(II)-coordinated water (wat1). The reaction initiates through a proton transfer to Glu219, followed by a nucleophilic attack by a zinc(II)-coordinated hydroxide anion nucleophile at the carbonyl carbon of the scissile bond, leading to the formation of a tetrahedral intermediate (IM2). The process continues with a hydrogen-bond rearrangement to facilitate proton transfer from wat2 to the amide nitrogen of the scissile bond and, finally, C-N bond cleavage. The calculations indicate that the rate-determining step is the water-mediated nucleophilic attack with an activation energy barrier of 22.3 kcal/mol. Furthermore, the calculations show that the hydrogen-bond rearrangement/proton-transfer step can proceed in a consecutive or concerted manner, depending on the conformation of the tetrahedral intermediate, with the consecutive mechanism being energetically preferable. Overall, the study reveals the crucial role of a second water molecule and the dynamics for effective MMP-1-catalyzed collagenolysis.
Collapse
Affiliation(s)
- Ann Varghese
- Department
of Chemistry, Michigan Technological University, Houghton, Michigan 49931, United States
| | - Sodiq O. Waheed
- Department
of Chemistry, Michigan Technological University, Houghton, Michigan 49931, United States
| | - Koteswararao Gorantla
- Department
of Chemistry, Michigan Technological University, Houghton, Michigan 49931, United States
| | - Isabella DiCastri
- Department
of Chemical Engineering, Michigan Technological
University, Houghton, Michigan 49931, United States
| | - Ciara LaRouche
- Department
of Chemical Engineering, Michigan Technological
University, Houghton, Michigan 49931, United States
| | - Brendan Kaski
- Department
of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan 49931, United States
| | - Gregg B. Fields
- Department
of Chemistry and Biochemistry and I-HEALTH, Florida Atlantic University, Jupiter, Florida 33458, United States
| | | |
Collapse
|
8
|
Compounds in Indonesian Ginger Rhizome Extracts and Their Potential for Anti-Skin Aging Based on Molecular Docking. COSMETICS 2022. [DOI: 10.3390/cosmetics9060128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Skin aging is a condition caused by reactive oxygen species (ROS) and advanced glycation end products (AGEs). Indonesian gingers (Zingiber officinale), which consists of Gajah (GG), Red (MM), and Emprit (EE) ginger, are thought to produce anti-skin aging compounds through enzyme inhibition. The enzymes used in the molecular docking study were collagenase, hyaluronidase, elastase, and tyrosinase. This study aimed to determine the compounds contained in Indonesian ginger rhizome ethanolic extracts using liquid chromatography–mass spectrometry/mass spectrometry to differentiate metabolites contained in the different Indonesian ginger rhizome extracts. A principal component analysis (PCA) and a heat map analysis were used in order to determine which compounds and extracts contained potential anti-skin aging properties based on a molecular docking study. Ascorbic acid was used as a control ligand in the molecular docking study. Ninety-eight compounds were identified in three different ginger rhizomes extracts and were grouped into three separate quadrants. The most potent compound for anti-skin aging in the Indonesian ginger rhizome extracts was octinoxate. Octinoxate showed a high abundance in the EE ginger rhizome extract. Therefore, the EE ginger extract was the Indonesian ginger rhizome extract with the greatest potential for anti-skin aging.
Collapse
|
9
|
Matysiak J, Packi K, Klimczak S, Bukowska P, Matuszewska E, Klupczyńska-Gabryszak A, Bręborowicz A, Matysiak J. Cytokine profile in childhood asthma. JOURNAL OF MEDICAL SCIENCE 2022. [DOI: 10.20883/medical.e725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Childhood asthma is a chronic airway disease, which pathogenesis is markedly heterogeneous–with multiple phenotypes defining visible characteristics and endotypes defining molecular mechanisms. Cytokines and chemokines released during inflammatory responses are key immune mediators. The cytokine response can largely determine the susceptibility to childhood asthma and its severity. The purpose of this study was to characterize the immune profile of childhood asthma. The study involved 26 children (3–18 years old), who were divided into 2 groups: study–with childhood asthma; control–without asthma. The innovative Bio-Plex method was used to determine the serum concentration of 37 inflammatory proteins in one experiment. The results were analyzed using univariate statistical tests. In the study group, the level of the 10 tested markers increased, while the level of the remaining 9 decreased compared to the control; a statistically significant reduction in concentration was obtained only for the MMP-1(p<0.05). According to the ROC curve, MMP-1 can be considered an effective discriminator of childhood asthma (p<0.05; AUC=0.752). Cytokines/chemokines may be useful in the diagnosis of childhood asthma and may also become a prognostic target in determining the phenotype/endotype of this condition. This study should be a prelude to and an incentive for more complex proteomic analyzes.
Collapse
|
10
|
Jeong HD, Kim JH, Kwon GE, Lee ST. Expression of Polyamine Oxidase in Fibroblasts Induces MMP-1 and Decreases the Integrity of Extracellular Matrix. Int J Mol Sci 2022; 23:ijms231810487. [PMID: 36142401 PMCID: PMC9504367 DOI: 10.3390/ijms231810487] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 09/02/2022] [Accepted: 09/07/2022] [Indexed: 11/16/2022] Open
Abstract
Polyamine oxidase (PAOX) (N1-acetylpolyamine oxidase) is a major enzyme in the polyamine catabolism pathway that generates hydrogen peroxide. Hydrogen peroxide plays a crucial role in skin aging via extracellular matrix (ECM) degradation by increasing the matrix metalloproteinase-1 (MMP-1) levels. We analyzed the integrity of the ECM in foreskin fibroblasts using PAOX expression. PAOX increased the MMP-1 secretion and type Ι collagen degradation in 2D and 3D cultures of fibroblasts, respectively. Similarly, PAOX overexpression increased the messenger ribonucleic acid (mRNA) level of MMP-1. PAOX expression induced polyamine catabolism, decreased the spermine levels, and increased the putrescine levels. However, the exogenous polyamine treatment did not change the MMP-1 and type I collagen levels as much as PAOX expression. PAOX expression increased the reactive oxygen species (ROS) production in fibroblasts, and exogenous hydrogen peroxide increased both the ROS production and MMP-1 secretion. Furthermore, N-acetylcysteine, an antioxidant, reversed the PAOX-induced ROS production and MMP-1 secretion. PAOX induced the signaling pathways that activate activator protein-1 (AP-1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), which are important transcription factors for MMP-1 transactivation. We concluded that PAOX increased the ROS levels in fibroblasts, leading to an increase in MMP-1 expression. Therefore, we propose that PAOX is a potential target molecule in protecting the ECM integrity.
Collapse
Affiliation(s)
- Hae Dong Jeong
- Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea
| | - Jin Hyung Kim
- Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea
| | - Go Eun Kwon
- Molecular Recognition Research Center, Korea Institute of Science and Technology, Seoul 02792, Korea
| | - Seung-Taek Lee
- Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea
- Correspondence: ; Tel.: +82-221232703
| |
Collapse
|
11
|
Kao CC, Hsu HE, Lai JC, Chen HC, Chuang SW, Lee MC. Strategy to Estimate Sample Sizes to Justify the Association between MMP1 SNP and Osteoarthritis. Genes (Basel) 2022; 13:genes13061084. [PMID: 35741844 PMCID: PMC9222496 DOI: 10.3390/genes13061084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 06/16/2022] [Accepted: 06/16/2022] [Indexed: 12/04/2022] Open
Abstract
Background: the impact of knee osteoarthritis (OA) poses a formidable challenge to older adults. Studies have reported that genetic factors, such as MMP1, are one of important risk factors for knee OA. Although the relationship between the genetic polymorphism of MMP1 rs1799750 and the risk of knee OA has been explored, conclusions have been nonunanimous and pending due to research sample sizes, one of determinants in studying genetic polymorphisms associated with disease. Objective: to establish a model to assess whether the genetic polymorphism of MMP1 rs1799750 is associated with knee OA based on an estimation of sample sizes. Methods: samples were collected from a case−control and meta-analysis study. In the case−control study, patients who underwent knee X-ray examinations based on the Kellgren−Lawrence Grading System (KL) as diagnostic criteria were recruited at the Health Examination Center of the Tri-Service General Hospital from 2015 to 2019. Gene sequencing was conducted using iPLEX Gold. Those with unsuccessful gene sequencing were excluded. Finally, there were 569 patients in the knee OA group (KL ≥ 2) and 534 participants in the control group (KL < 2). In the meta-analysis, we used the databases PubMed, EMBASE, and Cochrane to search for studies on the relationship between MMP1 rs1799750 and knee OA. Next, we adopted the trial sequential analysis (TSA) method to assess whether sample sizes were sufficient or not to determine the risk of the genetic polymorphism of MMP1 rs1799750 on knee OA in Caucasians and Asians. Results: in Caucasians, the MMP1 rs1799750 was not significantly associated with knee OA with an odds ratios (OR) of 1.10 (95% confidence interval, CI: 0.45−2.68). Some extra 8559 samples were needed to conclude this relationship in Caucasians by the TSA model. In Asians, neither our case−control study results (n = 1103) nor a combination of samples from the case−control and meta-analysis results showed an association between MMP1 rs1799750 and knee OA. The OR (95% CI) was 1.10 (0.81−1.49) in a combination of Asian samples. Some extra 5517 samples were needed to justify this relationship in Asians by the TSA model. Conclusions: this research shows that an extra 8559 and 5517 samples are needed in Caucasians and Asians, respectively, in order to justify the association between MMP1 rs1799750 and knee OA.
Collapse
Affiliation(s)
- Chung-Cheng Kao
- Tri-Service General Hospital Songshan Branch, National Defense Medical Center, Taipei 10581, Taiwan;
| | - Hsiang-En Hsu
- School of Public Health, National Defense Medical Center, Taipei 11490, Taiwan; (H.-E.H.); (S.-W.C.)
| | - Jen-Chieh Lai
- Orthopaedic Department, Armed Forces General Hospital, Taichung 41152, Taiwan;
- School of Medicine, National Defense Medical Center, Taipei 11490, Taiwan
| | - Hsiang-Cheng Chen
- Division of Rheumatology/Immunology/Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan;
| | - Su-Wen Chuang
- School of Public Health, National Defense Medical Center, Taipei 11490, Taiwan; (H.-E.H.); (S.-W.C.)
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan
| | - Meng-Chang Lee
- School of Public Health, National Defense Medical Center, Taipei 11490, Taiwan; (H.-E.H.); (S.-W.C.)
- Correspondence:
| |
Collapse
|
12
|
Wang J, Zhao X, Tian G, Liu X, Gui C, Xu L. Down-Regulation of miR-138 Alleviates Inflammatory Response and Promotes Wound Healing in Diabetic Foot Ulcer Rats via Activating PI3K/AKT Pathway and hTERT. Diabetes Metab Syndr Obes 2022; 15:1153-1163. [PMID: 35444435 PMCID: PMC9015052 DOI: 10.2147/dmso.s359759] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 04/01/2022] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVE To study the role of miR-138 on the repair of diabetic foot ulcer (DFU) and further to explore its possible mechanism. MATERIALS AND METHODS miR-138 inhibitor, IGF-1, LY294002 were used in DFU rat mode, and the mRNA expression of miR-138 was detected. HE staining was used to observe the histological changes of skin ulcer in rats. The level of inflammation, wound healing, and blood vessel formation-related factors were detected by ELISA and immunohistochemical. The expression of VEGF and PI3K/AKT pathway-related proteins were detected by Western blot. To further determine the underlying mechanism of miR-138 in the repair of DFU, telomerase inhibitor BIBR-1232 was used in HUVECs. Dual-luciferase assay was used to determine the target relationship between miR-138 and hTERT. CCK-8, transwell, and tube formation assays were conducted to observe the biological behavior of HUVECs. Inflammatory cytokines and PI3K/AKT pathway-related proteins were also measured by ELISA and Western blot. RESULTS The mRNA expression of miR-138 in DFU rat was increased and ulcer of diabetic foot rats was improved after silencing miR-138. The results of cellular bioactivity in vitro experiment were consistent with that in vivo. Meanwhile, after silencing miR-138, the level of inflammatory cytokines was decreased, while the level of anti-inflammatory and healing factors was increased in vivo and vitro. Moreover, the ratios of p-PI3K/PI3K and p-AKT/AKT were upregulated after treated with miR-138 inhibitor and miR-138 was negatively regulated the expression of hTERT. However, the inhibitory effect on inflammatory response and the promotion effect on wound healing of miR-138 inhibitor were reversed by LY294002 and BIBR-1232. CONCLUSION Down-regulation of miR-138 could alleviate inflammatory response and promote wound healing in DFU rats by activating PI3K/AKT pathway and hTERT.
Collapse
Affiliation(s)
- Jian Wang
- School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, 250012, People’s Republic of China
- Department of Orthopedics, Qufu Hospital of TCM, Qufu, 273100, People’s Republic of China
| | - Xiaodan Zhao
- Image Center, Shandong Provincial Third Hospital, Jinan, 250000, People’s Republic of China
| | - Guichang Tian
- Department of Orthopedics, Qufu Hospital of TCM, Qufu, 273100, People’s Republic of China
| | - Xiaochao Liu
- Department of Orthopedics, Qufu Hospital of TCM, Qufu, 273100, People’s Republic of China
| | - Chengyan Gui
- Department of Orthopedics, Qufu Hospital of TCM, Qufu, 273100, People’s Republic of China
| | - Lin Xu
- School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, 250012, People’s Republic of China
- Department of Orthopedics, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, 264100, People’s Republic of China
- Correspondence: Lin Xu, Department of Orthopedics, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, 264100, People’s Republic of China, Tel +86-13805350031, Email ;
| |
Collapse
|
13
|
Baidya SK, Amin SA, Jha T. Outline of gelatinase inhibitors as anti-cancer agents: A patent mini-review for 2010-present. Eur J Med Chem 2020; 213:113044. [PMID: 33279289 DOI: 10.1016/j.ejmech.2020.113044] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 10/15/2020] [Accepted: 11/18/2020] [Indexed: 12/25/2022]
Abstract
Matrix metalloproteinases (MMPs) are involved in several pathological and physiological functions. Gelatinases (MMP-2 and -9) have significant attention as therapeutic targets against cancer. Gelatinase inhibitors have demonstrated their effectiveness in several diseases including cancer. However, it is quite a challenging task to develop inhibitors as a therapeutic agent. This review summarizes the patent dedicated to the medicinal chemistry of gelatinase inhibitor reported over last decades. We examine the patent being pursued for gelatinase inhibitor development to highlight the key issues. The main aim is to provide the scientific community with an overview of the patented gelatinase inhibitors to allow further development. During early 2000s, some MMP inhibitors failed to pass the clinical trials. Hence, the lessons learned from early evidence and recent knowledge in that field will rejuvenate the development of selective inhibitors. Various studies and patents have continued in the recent years to expand knowledge. Continuously, our research team has been involved in the design of potent and selective gelatinase inhibitors for the past few years. This study is a part of our efforts. This study may be beneficial in the design and development of better gelatinase inhibitors in the future.
Collapse
Affiliation(s)
- Sandip Kumar Baidya
- Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, P. O. Box 17020, Jadavpur University, Kolkata, 700032, West Bengal, India.
| | - Sk Abdul Amin
- Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, P. O. Box 17020, Jadavpur University, Kolkata, 700032, West Bengal, India.
| | - Tarun Jha
- Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, P. O. Box 17020, Jadavpur University, Kolkata, 700032, West Bengal, India.
| |
Collapse
|
14
|
Kim BS, Das S, Jang J, Cho DW. Decellularized Extracellular Matrix-based Bioinks for Engineering Tissue- and Organ-specific Microenvironments. Chem Rev 2020; 120:10608-10661. [PMID: 32786425 DOI: 10.1021/acs.chemrev.9b00808] [Citation(s) in RCA: 267] [Impact Index Per Article: 53.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Biomaterials-based biofabrication methods have gained much attention in recent years. Among them, 3D cell printing is a pioneering technology to facilitate the recapitulation of unique features of complex human tissues and organs with high process flexibility and versatility. Bioinks, combinations of printable hydrogel and cells, can be utilized to create 3D cell-printed constructs. The bioactive cues of bioinks directly trigger cells to induce tissue morphogenesis. Among the various printable hydrogels, the tissue- and organ-specific decellularized extracellular matrix (dECM) can exert synergistic effects in supporting various cells at any component by facilitating specific physiological properties. In this review, we aim to discuss a new paradigm of dECM-based bioinks able to recapitulate the inherent microenvironmental niche in 3D cell-printed constructs. This review can serve as a toolbox for biomedical engineers who want to understand the beneficial characteristics of the dECM-based bioinks and a basic set of fundamental criteria for printing functional human tissues and organs.
Collapse
Affiliation(s)
- Byoung Soo Kim
- Future IT Innovation Laboratory, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Namgu,, Pohang, Kyungbuk 37673, Republic of Korea.,POSTECH-Catholic Biomedical Engineering Institute, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Namgu, Pohang, Kyungbuk 37673, Republic of Korea
| | - Sanskrita Das
- Department of Creative IT Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Namgu, Pohang, Kyungbuk 37673, Republic of Korea
| | - Jinah Jang
- Future IT Innovation Laboratory, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Namgu,, Pohang, Kyungbuk 37673, Republic of Korea.,Department of Creative IT Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Namgu, Pohang, Kyungbuk 37673, Republic of Korea.,Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Namgu, Pohang, Kyungbuk 37673, Republic of Korea.,School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Namgu, Pohang, Kyungbuk 37673, Republic of Korea.,POSTECH-Catholic Biomedical Engineering Institute, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Namgu, Pohang, Kyungbuk 37673, Republic of Korea.,Institute of Convergence Science, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Dong-Woo Cho
- Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Namgu, Pohang, Kyungbuk 37673, Republic of Korea.,POSTECH-Catholic Biomedical Engineering Institute, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Namgu, Pohang, Kyungbuk 37673, Republic of Korea.,Institute of Convergence Science, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| |
Collapse
|
15
|
Rosales AS, Rodríguez EAV, González CLL, Arellano EDR, Rubio SAG, Cobián TAG. Association Between -1607 1G/2G Polymorphism of MMP1 and Temporomandibular Joint Anterior Disc Displacement with Reduction. Braz Dent J 2020; 31:152-156. [PMID: 32556014 DOI: 10.1590/0103-6440202003037] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Accepted: 11/06/2019] [Indexed: 11/22/2022] Open
Abstract
Anterior disc displacement with reduction (DDWR) is considered one of the most common disorders within the temporomandibular joint (TMJ), with a prevalence of 41% in adults. Matrix metalloproteinases play an important role in the degradation of the TMJ and the matrix metalloproteinase 1 (MMP1) 1607 1G/2G polymorphism increases the local expression of MMP1 thus leading to accelerated degradation of the extracellular matrix. The objective of this study was to evaluate the association between the 1607 1G/2G polymorphism of MMP1 gene and DDWR in a group of Mexican individuals from western Mexico. A total of 67 unrelated individuals, between the ages of 18 and 36 years, of both genders, were included in this study. Study participants with DDWR were required to meet the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD), while a second control group of 90 individuals without DDWR were also included. Both groups were required to have paternal and maternal ancestry (grandparents) of the same geographic and ethnic region. Genotypes were determined using the nested PCR technique. The 1G/2G polymorphism was found in 68.7%, followed by 2G/2G in 25.4% and 1G/1G in 6.0% of the cases group. While the prevalence in the control group was 55.5% for the 1G/2G polymorphism, 26.6% for 1G/1G and 17.7% for 2G/2G. An association was found between the 2G allele of the 1607 1G/2G polymorphism of MMP1 gene and the presence of DDWR in the patients of western Mexico.
Collapse
Affiliation(s)
- Alberto Sierra Rosales
- Departamento de Clínicas Odontológicas Integrales, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara
| | | | - Christian Lorena López González
- Instituto de Terapéutica Experimental y Clínica, CUCS - Centro Universitario de Ciencias de la Salud; Universidad de Guadalajara
| | - Edy David Rubio Arellano
- Instituto de Terapéutica Experimental y Clínica, CUCS - Centro Universitario de Ciencias de la Salud; Universidad de Guadalajara
| | - Susan Andrea Gutiérrez Rubio
- Instituto de Terapéutica Experimental y Clínica, CUCS - Centro Universitario de Ciencias de la Salud; Universidad de Guadalajara
| | - Teresa Arcelia García Cobián
- Instituto de Terapéutica Experimental y Clínica, CUCS - Centro Universitario de Ciencias de la Salud; Universidad de Guadalajara
| |
Collapse
|
16
|
Schon J, Chahla J, Paudel S, Manandhar L, Feltham T, Huard J, Philippon M, Zhang Z. Expression profile of matrix metalloproteinases in the labrum of femoroacetabular impingement. Bone Joint Res 2020; 9:173-181. [PMID: 32431808 PMCID: PMC7229337 DOI: 10.1302/2046-3758.94.bjr-2019-0083.r1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Aims Femoroacetabular impingement (FAI) is a potential cause of hip osteoarthritis (OA). The purpose of this study was to investigate the expression profile of matrix metalloproteinases (MMPs) in the labral tissue with FAI pathology. Methods In this study, labral tissues were collected from four FAI patients arthroscopically and from three normal hips of deceased donors. Proteins extracted from the FAI and normal labrums were separately applied for MMP array to screen the expression of seven MMPs and three tissue inhibitors of metalloproteinases (TIMPs). The expression of individual MMPs and TIMPs was quantified by densitometry and compared between the FAI and normal labral groups. The expression of selected MMPs and TIMPs was validated and localized in the labrum with immunohistochemistry. Results On MMP arrays, most of the targeted MMPs and TIMPs were detected in the FAI and normal labral proteins. After data normalization, in comparison with the normal labral proteins, expression of MMP-1 and MMP-2 in the FAI group was increased and expression of TIMP-1 reduced. The histology of the FAI labrum showed disorderly cell distribution and altered composition of thick and thin collagen fibres. The labral cells expressing MMP-1 and MMP-2 were localized and their percentages were increased in the FAI labrum. Immunohistochemistry confirmed that the percentage of TIMP-1 positive cells was reduced in the FAI labrum. Conclusion This study established an expression profile of MMPs and TIMPs in the FAI labrum. The increased expression of MMP-1 and MMP-2 and reduced expression of TIMP-1 in the FAI labrum are indicative of a pathogenic role of FAI in hip OA development. Cite this article:Bone Joint Res. 2020;9(4):173–181.
Collapse
Affiliation(s)
- Jason Schon
- Steadman Philippon Research Institute, Vail, Colorado, USA; Albany Medical College, Albany, New York, New York, USA
| | - Jorge Chahla
- Steadman Philippon Research Institute, Vail, Colorado, USA; Assistant Professor, Rush University Medical Center, Chicago, Illinois, USA
| | - Sharada Paudel
- MedStar Union Memorial Hospital, Baltimore, Maryland, USA
| | | | - Tyler Feltham
- MedStar Union Memorial Hospital, Baltimore, Maryland, USA
| | - Johnny Huard
- Steadman Philippon Research Institute, Vail, Colorado, USA; The Steadman Clinic, Vail, Colorado, USA
| | - Marc Philippon
- Steadman Philippon Research Institute, Vail, Colorado, USA; The Steadman Clinic, Vail, Colorado, USA
| | - Zijun Zhang
- MedStar Union Memorial Hospital, Baltimore, Maryland, USA; Director, Orthopaedic Innovation Center, Mercy Medical Center, Baltimore, Maryland, USA
| |
Collapse
|
17
|
Takebayashi K, Nasu K, Okamoto M, Aoyagi Y, Hirakawa T, Narahara H. hsa-miR-100-5p, an overexpressed miRNA in human ovarian endometriotic stromal cells, promotes invasion through attenuation of SMARCD1 expression. Reprod Biol Endocrinol 2020; 18:31. [PMID: 32299427 PMCID: PMC7161200 DOI: 10.1186/s12958-020-00590-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Accepted: 04/13/2020] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND A number of microRNAs are aberrantly expressed in endometriosis and are involved in its pathogenesis. Our previous study demonstrated that has-miR-100-5p expression is enhanced in human endometriotic cyst stromal cells (ECSCs). The present study aimed to elucidate the roles of has-miR-100-5p in the pathogenesis of endometriosis. METHODS Normal endometrial stromal cells (NESCs) were isolated from normal eutopic endometrium without endometriosis. Using hsa-miR-100-5p-transfected NESCs, we evaluated the effect of hsa-miR-100-5p on the invasiveness of these cells by Transwell invasion assay and in-vitro wound repair assay. We also investigated the downstream signal pathways of hsa-miR-100-5p by microarray analysis and Ingenuity pathways analysis. RESULTS hsa-miR-100-5p transfection enhanced the invasion and motility of NESCs. After hsa-miR-100-5p transfection, mRNA expression of SWItch/sucrose non-fermentable-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1 (SMARCD1) was significantly attenuated. Whereas, the expression of matrix metallopeptidase 1 (MMP1) mRNA and active MMP1 protein levels was upregulated. CONCLUSION We found that SMARCD1/MMP-1 is a downstream pathway of hsa-miR-100-5p. hsa-miR-100-5p transfection enhanced the motility of NESCs by inhibiting SMARCD1 expression and MMP1 activation. These findings suggest that enhanced hsa-miR-100-5p expression in endometriosis is involved in promoting the acquisition of endometriosis-specific characteristics during endometriosis development. Our present findings on the roles of hsa-miR-100-5p may thus contribute to understand the epigenetic mechanisms involved in the pathogenesis of endometriosis.
Collapse
Affiliation(s)
- Kanetoshi Takebayashi
- Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Idaigaoka 1-1, Hasama-machi, Yufu-shi, Oita, 879-5593, Japan
| | - Kaei Nasu
- Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Idaigaoka 1-1, Hasama-machi, Yufu-shi, Oita, 879-5593, Japan.
- Division of Obstetrics and Gynecology, Support System for Community Medicine, Faculty of Medicine, Oita University, Oita, Japan.
| | - Mamiko Okamoto
- Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Idaigaoka 1-1, Hasama-machi, Yufu-shi, Oita, 879-5593, Japan
| | - Yoko Aoyagi
- Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Idaigaoka 1-1, Hasama-machi, Yufu-shi, Oita, 879-5593, Japan
| | - Tomoko Hirakawa
- Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Idaigaoka 1-1, Hasama-machi, Yufu-shi, Oita, 879-5593, Japan
| | - Hisashi Narahara
- Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Idaigaoka 1-1, Hasama-machi, Yufu-shi, Oita, 879-5593, Japan
| |
Collapse
|
18
|
Hammouda MB, Ford AE, Liu Y, Zhang JY. The JNK Signaling Pathway in Inflammatory Skin Disorders and Cancer. Cells 2020; 9:E857. [PMID: 32252279 PMCID: PMC7226813 DOI: 10.3390/cells9040857] [Citation(s) in RCA: 172] [Impact Index Per Article: 34.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 03/21/2020] [Accepted: 03/26/2020] [Indexed: 02/07/2023] Open
Abstract
The c-Jun N-terminal kinases (JNKs), with its members JNK1, JNK2, and JNK3, is a subfamily of (MAPK) mitogen-activated protein kinases. JNK signaling regulates a wide range of cellular processes, including cell proliferation, differentiation, survival, apoptosis, and inflammation. Dysregulation of JNK pathway is associated with a wide range of immune disorders and cancer. Our objective is to provide a review of JNK proteins and their upstream regulators and downstream effector molecules in common skin disorders, including psoriasis, dermal fibrosis, scleroderma, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma.
Collapse
Affiliation(s)
- Manel B. Hammouda
- Department of Dermatology, Duke University Medical Center, Durham, NC 27710, USA; (M.B.H.); (A.E.F.); (Y.L.)
| | - Amy E. Ford
- Department of Dermatology, Duke University Medical Center, Durham, NC 27710, USA; (M.B.H.); (A.E.F.); (Y.L.)
| | - Yuan Liu
- Department of Dermatology, Duke University Medical Center, Durham, NC 27710, USA; (M.B.H.); (A.E.F.); (Y.L.)
| | - Jennifer Y. Zhang
- Department of Dermatology, Duke University Medical Center, Durham, NC 27710, USA; (M.B.H.); (A.E.F.); (Y.L.)
- Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
| |
Collapse
|
19
|
Gimeno A, Beltrán-Debón R, Mulero M, Pujadas G, Garcia-Vallvé S. Understanding the variability of the S1′ pocket to improve matrix metalloproteinase inhibitor selectivity profiles. Drug Discov Today 2020; 25:38-57. [DOI: 10.1016/j.drudis.2019.07.013] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 06/23/2019] [Accepted: 07/26/2019] [Indexed: 12/15/2022]
|
20
|
Xu B, Xing RL, Zhang L, Huang ZQ, Zhang NS, Mao J. Effects of MMP-1 1G/2G polymorphism on osteoarthritis: A meta-analysis study. ACTA ORTHOPAEDICA ET TRAUMATOLOGICA TURCICA 2019; 53:129-133. [PMID: 30691874 PMCID: PMC6506809 DOI: 10.1016/j.aott.2018.12.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/05/2018] [Revised: 12/07/2018] [Accepted: 12/30/2018] [Indexed: 12/11/2022]
Abstract
Objective The aim of this meta-analysis was to clarify the role of Matrix metalloproteinase 1 (MMP-1) -1607 1G/2G (rs1799750) polymorphism on the osteoarthritis (OA) risk. Methods Articles were selected by retrieving the Web of Science, Embase and Pubmed. The strength of the association between -1607 1G/2G polymorphism and OA risk was assessed by odds ratios (ORs) with the corresponding 95% confidence interval (CI) for each study. Results No significant association between -1607 1G/2G polymorphism and OA risk was found in all the models overall (2G2G vs 1G1G, OR (95%CI) = 0.69 (0.36–1.32), P = 0.54; 2G2G + 2G1G vs 1G1G, OR (95%CI) = 0.88 (0.47–1.63), P = 0.69; 2G2G vs 2G1G + 1G1G, OR (95%CI) = 1.30 (0.68–2.47), P = 0.41; 2 G vs 1G, OR (95%CI) = 0.90 (0.86–1.54), P = 0.66). By subgroup analysis, significant association was found in the “< 60 years” group (2G2G vs 1G1G, OR (95%CI) = 3.46 (2.13–5.62), P = 0.00; 2G2G + 2G1G vs 1G1G, OR (95%CI) = 0.49 (0.31–0.79), P = 0.00; 2G2G vs 2G1G + 1G1G, OR (95%CI) = 2.74 (1.80–4.16, P = 0.00; 2 G vs 1G, OR (95%CI) = 0.56 (0.35–0.89), P = 0.01). Conclusions This meta-analysis showed that -1607 1G/2G polymorphism may increase the susceptibility to OA among the younger populations (<60 years). More studies with detailed information are needed to validate our conclusion. Level of Evidence Level I Diagnostic Study.
Collapse
|
21
|
Ju F, Li N, Wang W, Yuan H. Effects of varying radiation dosages on MMP1 expression, and MMP1 knockdown on the viability and migration of SW620 cells. Mol Med Rep 2019; 19:2503-2508. [PMID: 30720073 PMCID: PMC6423606 DOI: 10.3892/mmr.2019.9899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Accepted: 10/10/2018] [Indexed: 11/10/2022] Open
Abstract
Colorectal cancer (CRC), also known as bowel cancer, is one of the leading causes of cancer-associated mortality worldwide at present. The aim of the present study was to detect the effects of matrix metalloproteinase 1 (MMP1) on the viability and migration of a CRC cell line in the presence or absence of variation X-ray radiation doses. The CRC cell line, SW620, was cultured and treated with different X-ray doses (0, 0.1, 0.5, 1, 3 and 6 Gy). MMP1 expression was downregulated via the application of a specific small interfering (si)-RNA. The viability and migration of SW620 cells prior to and following transfection were detected with MTT and Transwell chamber assays, respectively. The application of siRNA transfection to silence MMP1 in SW620 cells resulted in reduced cell viability and migration (P<0.05). Compared with the control, the cell viability and migration of cells were significantly reduced when exposed to 0.5, 1, 3, and 6 Gy X-ray radiation (P<0.05). In SW620 cells treated with different X-ray doses, the mRNA expression levels of MMP1 were significantly reduced (P<0.05). Cells treated with 0.5 Gy X-ray exposure exhibited the lowest mRNA expression levels of MMP1 when compared with other doses of X-ray radiation. The expression of MMP1 was associated with the promotion of the viability and migration of SW620 cells. X-ray radiation with 6 Gy dosages significantly reduced cell viability when compared with the control. Thus, MMP1-targeted therapy combined with radiotherapy could be used for treating CRC.
Collapse
Affiliation(s)
- Fang Ju
- Department of Oncology, Qingdao Central Hospital, Qingdao, Shandong 266042, P.R. China
| | - Na Li
- Department of Respiratory Medicine, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
| | - Wenming Wang
- Department of Oncology, Qingdao Central Hospital, Qingdao, Shandong 266042, P.R. China
| | - Haicheng Yuan
- Department of Neurology, Qingdao Central Hospital, Qingdao, Shandong 266042, P.R. China
| |
Collapse
|
22
|
Eguia Del Valle A, López-Vicente J, Martínez-Conde R, Aguirre-Zorzano LA. Current understanding of genetic polymorphisms as biomarkers for risk of biological complications in implantology. J Clin Exp Dent 2018; 10:e1029-e1039. [PMID: 30386510 PMCID: PMC6203903 DOI: 10.4317/jced.55141] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Accepted: 08/06/2018] [Indexed: 01/01/2023] Open
Abstract
Background In the last decade, multiple studies have been published that analyze the relationship between the risk of experiencing biological complications with implants and the presence of certain types of genetic polymorphisms. In the present report, we analyze the controversies that have arisen from this important area of investigation and synthesize the most prominent aspects of knowledge related to this possible etiopathogenic relationship. Material and Methods For this review, the biomedical databases PubMed-Medline, SciELO, and DOAJ were used. Different search strategies were employed, from which 298 articles initially emerged. After refinement of the search, 55 articles published between 2002 and 2018 were finally selected based on relevance. Results In certain population groups, there is evidence to support that about a dozen polymorphisms could in some way be related to biological complications in implantology. Indeed, the results may vary according to the ethnic origin of the population studied. Most of the published investigations are initial studies reporting small sample sizes and utilizing different study group homogenization methods. We are still at a preliminary stage of our understanding and development with regard to these types of biomarkers. The interesting results identified indicate that new investigations will be necessary to eliminate the biases observed in some studies and to homogenize the research groups. In order to clarify the controversies surrounding the current knowledge in this field, we believe that it will be necessary to employ larger study groups and search for possible synergistic effects between different polymorphisms. Key words:Polymorphism, genetic markers, peri-implantitis, biological complication, dental implant.
Collapse
Affiliation(s)
- Asier Eguia Del Valle
- Associate Professor. DDS, PhD.Departamento Estomatología II, Facultad de Medicina y Enfermería. Universidad del País Vasco (UPV/EHU). // Stomatology II Department, Faculty of Medicine and Nursering. University of the Basque country (UPV/EHU). Leioa (Vizcaya) Spain
| | - José López-Vicente
- Associate Professor. MD, DDS, PhD, Departamento Estomatología II, Facultad de Medicina y Enfermería. Universidad del País Vasco (UPV/EHU). // Stomatology II Department, Faculty of Medicine and Nursering. University of the Basque country (UPV/EHU). Leioa (Vizcaya) Spain
| | - Rafael Martínez-Conde
- Professor. MD, DDS, PhD, Departamento Estomatología II, Facultad de Medicina y Enfermería. Universidad del País Vasco (UPV/EHU). // Stomatology II Department, Faculty of Medicine and Nursering. University of the Basque country (UPV/EHU). Leioa (Vizcaya) Spain
| | - Luis-Antonio Aguirre-Zorzano
- Professor. MD,DDs, PhD. Departamento Estomatología II, Facultad de Medicina y Enfermería. Universidad del País Vasco (UPV/EHU). // Stomatology II Department, Faculty of Medicine and Nursering. University of the Basque country (UPV/EHU). Leioa (Vizcaya) Spain. Director of Master of Periodontology at the University of The Basque Country
| |
Collapse
|
23
|
MMP-1 overexpression selectively alters inhibition in D1 spiny projection neurons in the mouse nucleus accumbens core. Sci Rep 2018; 8:16230. [PMID: 30385861 PMCID: PMC6212422 DOI: 10.1038/s41598-018-34551-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 10/19/2018] [Indexed: 11/24/2022] Open
Abstract
Protease activated receptor-1 (PAR-1) and its ligand, matrix metalloproteinase-1 (MMP-1), are altered in several neurodegenerative diseases. PAR-1/MMP-1 signaling impacts neuronal activity in various brain regions, but their role in regulating synaptic physiology in the ventral striatum, which is implicated in motor function, is unknown. The ventral striatum contains two populations of GABAergic spiny projection neurons, D1 and D2 SPNs, which differ with respect to both synaptic inputs and projection targets. To evaluate the role of MMP-1/PAR-1 signaling in the regulation of ventral striatal synaptic function, we performed whole-cell recordings (WCR) from D1 and D2 SPNs in control mice, mice that overexpress MMP-1 (MMP-1OE), and MMP-1OE mice lacking PAR-1 (MMP-1OE/PAR-1KO). WCRs from MMP1-OE mice revealed an increase in spontaneous inhibitory post-synaptic current (sIPSC), miniature IPSC, and miniature excitatory PSC frequency in D1 SPNs but not D2 SPNs. This alteration may be partially PAR-1 dependent, as it was not present in MMP-1OE/PAR-1KO mice. Morphological reconstruction of D1 SPNs revealed increased dendritic complexity in the MMP-1OE, but not MMP-1OE/PAR-1KO mice. Moreover, MMP-1OE mice exhibited blunted locomotor responses to amphetamine, a phenotype also observed in MMP-1OE/PAR-1KO mice. Our data suggest PAR-1 dependent and independent MMP-1 signaling may lead to alterations in striatal neuronal function.
Collapse
|
24
|
Gantala SR, Kondapalli MS, Kummari R, Padala C, Tupurani MA, Kupsal K, Galimudi RK, Gundapaneni KK, Puranam K, Shyamala N, Guditi S, Rapur R, Hanumanth SR. Collagenase-1 (-1607 1G/2G), Gelatinase-A (-1306 C/T), Stromelysin-1 (-1171 5A/6A) functional promoter polymorphisms in risk prediction of type 2 diabetic nephropathy. Gene 2018; 673:22-31. [DOI: 10.1016/j.gene.2018.06.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 05/26/2018] [Accepted: 06/04/2018] [Indexed: 11/27/2022]
|
25
|
Hu W, Ye Y, Yin Y, Sang P, Li L, Wang J, Wan W, Li R, Bai X, Xie Y, Meng Z. Association of matrix metalloprotease 1, 3, and 12 polymorphisms with rheumatic heart disease in a Chinese Han population. BMC MEDICAL GENETICS 2018; 19:27. [PMID: 29458338 PMCID: PMC5819250 DOI: 10.1186/s12881-018-0538-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Accepted: 01/30/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND Rheumatic heart disease (RHD) is an autoimmune disease triggered by acute rheumatic fever (ARF). Matrix metalloproteinases (MMPs) play an important role in the modulation of immune responses. The purpose of this study was to evaluate the association of MMP1, 3, and 12 promoter polymorphisms with RHD in a Han population in Southern China since the 3 genes are localized on the same chromosome and have a combined effect. METHODS DNA samples were obtained from 90 adult patients with RHD and 90 control subjects. Polymorphisms in MMP1 (rs1799750), MMP3 (rs3025058), and MMP12 (rs2276109) were genotyped by direct sequencing. Differences in genotype and allele frequencies of these polymorphisms were compared between the cases and the controls using Unconditional logistic regression models and Chi-squared test. RESULTS The 2G/2G genotype of rs1799750 in MMP1 was associated with a significantly higher risk of RHD when compared with the 1G/1G genotype (OR = 3.227; 95% CI:1.118-9.31; p = 0.03). The frequency of allele 2G was higher in patients with RHD compared to the controls (69.4% vs. 58.9%; p = 0.048) No significant differences in genotype and allele frequencies of rs3025058 in MMP3 and rs2276109 in MMP12 were found between the patients with RHD and the controls (p > 0.05). CONCLUSIONS Our results suggest that rs1799750 in MMP1 might be a risk factor for RHD in a Han population in Southern China, and individuals carrying the 2G/2G genotype are likely more susceptible to RHD. In contrast, rs3025058 in MMP3 and rs2276109 in MMP12 might not contribute to the risk of developing RHD in this population. Further studies with larger samples and other ethnic populations are required to confirm these findings.
Collapse
Affiliation(s)
- Wei Hu
- Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China
| | - Yujia Ye
- Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China
| | - Yirui Yin
- Yunnan Institute of Microbiology, Yunnan University, Kunming, 650091, China
| | - Peng Sang
- Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China
| | - Linhua Li
- Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China
| | - Jing Wang
- Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China
| | - Wen Wan
- Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China
| | - Rui Li
- Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China
| | - Xiangfeng Bai
- Department of Cardiovascular Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China
| | - Yuehui Xie
- Department of Mathematics and Computer Science, Basic Medical College, Kunming Medical University, Kunming, 650500, China.
| | - Zhaohui Meng
- Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China.
| |
Collapse
|
26
|
Li T, Lv Z, Jing JJ, Yang J, Yuan Y. Matrix metalloproteinase family polymorphisms and the risk of aortic aneurysmal diseases: A systematic review and meta-analysis. Clin Genet 2017; 93:15-32. [PMID: 28485889 DOI: 10.1111/cge.13050] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2017] [Revised: 05/01/2017] [Accepted: 05/03/2017] [Indexed: 01/04/2023]
Abstract
It has been suggested that matrix metalloproteinase (MMP) polymorphisms are associated with the pathogenesis of aortic aneurysmal diseases. In this study, we conducted a systematic review with an update meta-analysis to investigate the relationship between MMP family polymorphisms and aortic aneurysmal diseases. We systematically reviewed 24 polymorphisms in 8 MMP genes related to the risk of abdominal aortic aneurysm (AAA), thoracic AA or thoracic aortic dissection (TAD). A total of 19 case-control studies with 15 highly studied MMP polymorphisms were included in our meta-analysis. Our results suggested that MMP2rs243865, MMP3rs3025058, MMP13rs2252070 polymorphisms were significantly associated with AAA risk, MMP2rs11643630, MMP8rs11225395 polymorphisms were correlated with TAD risk, and MMP9rs3918242 under the dominant model could increase AAA risk in hospital-based subgroup. No associations with aortic aneurysmal diseases were identified for other polymorphisms assessed in our meta-analysis. In summary, some studied MMP polymorphisms associated with the risk of aortic aneurysmal diseases are potential predictive biomarkers for the clinical application. Moreover, other MMP polymorphisms with limited studies but relevant to aortic aneurysmal formation and progression need further prospective and large investigations to confirm results.
Collapse
Affiliation(s)
- T Li
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China.,Department of Cardiovascular Ultrasound, the First Affiliated Hospital of China Medical University, Shenyang, China
| | - Z Lv
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China
| | - J-J Jing
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China
| | - J Yang
- Department of Cardiovascular Ultrasound, the First Affiliated Hospital of China Medical University, Shenyang, China
| | - Y Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China
| |
Collapse
|
27
|
Zhou Y, Gao Q, He D, Deng A, Huang R, Li Y, Tan C, Guo C, Guo Q, Wang L, Yang G, Zhang H. Matrix metalloproteinase-1 promoter -1607 bp 1G/2G polymorphism associated with increased risk of spinal tuberculosis in Southern Chinese Han population. J Clin Lab Anal 2017; 31. [PMID: 28129430 DOI: 10.1002/jcla.22136] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2016] [Accepted: 12/12/2016] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Spinal tuberculosis is the most common form of musculoskeletal tuberculosis. The expression of matrix metalloproteinase-1 (MMP-1) is increased in cells with Mycobacterium tuberculosis infection. MMP-1 plays a curial role in extracellular matrix degradation during the progression of tuberculosis. Although the 1G/2G polymorphism in MMP-1-1607 influences its transcription, its role in spinal tuberculosis remains unknown. METHODS Healthy controls and patients with spinal tuberculosis of Han ethnicity were recruited between January 2010 and May 2016. The MMP-1-1607 1G/2G polymorphism was genotyped using the Sequenom mass Array polymorphism analysis system. RESULTS The genotypes of 1G/1G, 1G/2G, and 2G/2G were found in 13.7%, 53.6%, and 32.8% of patients, and 12.2%, 37.4%, and 50.4% of controls, respectively. The 1G/2G genotype were more common in cases than in controls (P=2.05E-04). The 1G allele showed an association with an increased risk for spinal tuberculosis when compared to 2G allele (P=.004). 1G genotypes, having at least one 1G allele, were associated with the risk of developing spinal tuberculosis (1G/1G+1G/2G vs 2G/2G: OR=2.084, 95%CI=1.401-3.100, P=2.65E-04). CONCLUSION 1G genotypes of the MMP-1-1607 may be associated with susceptibility to spinal tuberculosis in Southern Chinese Han population.
Collapse
Affiliation(s)
- Ying Zhou
- Department of Clinical Laboratory, The People's Hospital of Guangxi Autonomous Region, Nanning, China
| | - Qile Gao
- Department of Spine Surgery, Xiangya Spinal Surgery Center, Xiangya Hospital, Central South University, Changsha, China
| | - Dan He
- Department of Neurology, The First Hospital of Changsha, Changsha, China
| | - Ang Deng
- Department of Spine Surgery, Xiangya Spinal Surgery Center, Xiangya Hospital, Central South University, Changsha, China
| | - Rongfu Huang
- Department of Clinical Laboratory, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, China
| | - Yanbing Li
- Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, China
| | - Chunyan Tan
- Department of Clinical Laboratory, The People's Hospital of Guangxi Autonomous Region, Nanning, China
| | - Chaofeng Guo
- Department of Spine Surgery, Xiangya Spinal Surgery Center, Xiangya Hospital, Central South University, Changsha, China
| | - Qiang Guo
- Department of Spine Surgery, Xiangya Spinal Surgery Center, Xiangya Hospital, Central South University, Changsha, China
| | - Longjie Wang
- Department of Spine Surgery, Xiangya Spinal Surgery Center, Xiangya Hospital, Central South University, Changsha, China
| | - Guanteng Yang
- Department of Spine Surgery, Xiangya Spinal Surgery Center, Xiangya Hospital, Central South University, Changsha, China
| | - Hongqi Zhang
- Department of Spine Surgery, Xiangya Spinal Surgery Center, Xiangya Hospital, Central South University, Changsha, China
| |
Collapse
|
28
|
Shen Z, Asa SL, Ezzat S. Ikaros and its interacting partner CtBP target the metalloprotease ADAMTS10 to modulate pituitary cell function. Mol Cell Endocrinol 2017; 439:126-132. [PMID: 27815209 DOI: 10.1016/j.mce.2016.10.032] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2016] [Revised: 10/28/2016] [Accepted: 10/29/2016] [Indexed: 12/23/2022]
Abstract
We have previously described the expression and up-regulation of the C-terminal Binding Protein (CtBP) in response to pituitary hypoxia. This co-repressor interacts with the hematopoietic factor Ikaros to target several components implicated in cellular growth and apoptotic pathways. To identify common transcriptional pituitary targets we performed promoter arrays using Ikaros and CtBP chromatin immunoprecipitated (ChIP) DNA from pituitary AtT20 cells. This approach yielded a finite list of gene targets common to both transcription factors. Of these, the metalloprotease ADAMTS10 emerged as a validated target. We show the ability of Ikaros to bind the ADAMTS10 promoter, influence its transfected activity, and induce endogenous gene expression. ADAMTS10 is expressed in primary pituitary cells and is down-regulated in Ikaros null mice. Further, knockdown of ADAMTS10 in AtT20 cells recapitulates the impact of Ikaros deficiency on POMC/ACTH hormone expression. These results uncover a novel role for the metalloprotease ADAMTS10 in the pituitary. Additionally, they position this metalloprotease as a potential functional integrator of the Ikaros-CtBP chromatin remodeling network.
Collapse
Affiliation(s)
- Zhongyi Shen
- Dept. of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario M5G 2M9, Canada; University Health Network and the Ontario Cancer Institute, Toronto, Ontario M5G 2M9, Canada
| | - Sylvia L Asa
- Dept. of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario M5G 2M9, Canada; University Health Network and the Ontario Cancer Institute, Toronto, Ontario M5G 2M9, Canada
| | - Shereen Ezzat
- Dept. of Medicine, University of Toronto, Toronto, Ontario M5G 2M9, Canada; University Health Network and the Ontario Cancer Institute, Toronto, Ontario M5G 2M9, Canada.
| |
Collapse
|
29
|
Yu J, Zhou B, Yu H, Han J, Cui M, Zhang F, Wang G, Guo L, Gao W. Association between plasma ADAMTS-7 levels and severity of disease in patients with stable obstructive coronary artery disease. Medicine (Baltimore) 2016; 95:e5523. [PMID: 27902619 PMCID: PMC5134802 DOI: 10.1097/md.0000000000005523] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
The metalloproteinase family of a disintegrin and metalloproteinase with thrombospondin motifs-7 (ADAMTS-7) was reported to be a novel locus associated with human coronary artery disease. This study aimed to investigate plasma ADAMTS-7 levels in stable obstructive CAD patients and elucidate the relationship between plasma ADAMTS-7 levels and the severity of CAD assessed by the Syntax score.This was a single center cross-sectional study performed in 182 CAD patients. ELISA was used to measure plasma ADAMTS-7 levels. All patients were divided into subgroup according to the ADAMTS-7 median in this cohort: high group with ADAMTS-7 ≥0.99 ng/mL and low group with ADAMTS-7 <0.99 ng/mL. Furthermore, all patients were divided into tertiles according to their Syntax scores (low group: Syntax score ≤10.0; moderate group: 10.0 <Syntax score ≤18.0; high group: Syntax score >18.0). We followed up the participants continuously until the first major adverse cardiovascular event (MACE) for a mean time of 22.0 months.Plasma ADAMTS-7 levels in the high Syntax score group were significantly higher compared with the low Syntax score group (3.29 [0.08-26.3] ng/mL vs 1.24 [0.15-8.78] ng/mL, P = 0.010). Plasma ADAMTS-7 levels were significantly positively correlated with the Syntax score tertiles (r = 0.157, P = 0.035). Logistic regression analysis indicated that the plasma ADAMTS-7 level was one of the independent predictors for the Syntax score tertiles (B = 1.118, 95% CI: 1.194-7.830, P = 0.020), together with HbA1c (B = 0.946, 95% CI: 1.248-5.312, P = 0.010), uric acid (B = -0.019, 95% CI: 0.974-0.988, P<0.001), and coronary artery calcium score (B = -0.001, 95% CI: 0.998-0.999, P < 0.001). Compared with the low ADAMTS-7 group, the high ADAMTS-7 group had significantly higher Syntax score (17.10±8.42 vs 14.96 ± 8.11, P = 0.047). Kaplan-Meier analysis showed patients in the high plasma ADAMTS-7 group tend to have a lower event-free survival rate than patients in the low plasma ADAMTS-7 group, unfortunately, no difference was detected (86.8% vs 88.0%, log rank = 0.314, P = 0.575).The plasma ADAMTS-7 level was positively correlated with the Syntax score significantly. The elevated plasma ADAMTS-7 level may be involved in the severity of disease in patients with stable coronary artery disease.
Collapse
|
30
|
He M, Wang W, Han X, Huang W. Matrix metalloproteinase-1 rs1799750 polymorphism and glaucoma: A meta-analysis. Ophthalmic Genet 2016; 38:211-216. [PMID: 27428613 DOI: 10.1080/13816810.2016.1193877] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
PURPOSE Several studies indicated that -1607 1G/2G (rs1799750) polymorphism in matrix metalloproteinase-1 (MMP-1) promoter was correlated with glaucoma susceptibility, but the results remain controversial. We performed a meta-analysis to assess whether rs1799750 confers glaucoma risk. METHODS Eligible studies were retrieved by systematically searching Pubmed, Embase, Web of Science, and Chinese Biomedical database. The degree of correlation was expressed as odds ratios (ORs) and 95% confidence interval (CI). The measurements were pooled by fixed effect model or random effect model. RESULTS This meta-analysis included five case-control studies involving 1261 patients with glaucoma and 1089 controls. The pooled results showed a significant association between rs1799750 and glaucoma under the homozygote (OR = 1.71, 95% CI 1.12-2.62, p = 0.014), recessive (OR = 1.64, 95% CI 1.20-2.25, p = 0.002), and allelic (OR = 1.35, 95% CI 1.05-1.72, p = 0.017) models. Subgroup analyses showed that the rs1799750 was significantly associated with primary angle closure glaucoma under homozygote (OR = 2.23, 95% CI 1.03-4.83, p = 0.043) and allelic (OR = 1.61, 95% CI 1.07-2.42, P = 0.021) models, while it was significantly associated with primary open angle glaucoma (OR = 1.64, 95% CI 1.05-2.56, p = 0.030) and exfoliation glaucoma (OR = 1.42, 95% CI 1.02-1.97, p = 0.036) under recessive models. No evidence of publication bias was detected. CONCLUSIONS Meta-analysis of existing data showed that rs1799750 may affect individual susceptibility to glaucoma. Nevertheless, more studies with large sample size and various ethnicities are warranted in light of the limited studies.
Collapse
Affiliation(s)
- Miao He
- a Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology , Sun Yat-Sen University , Guangzhou , China
| | - Wei Wang
- a Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology , Sun Yat-Sen University , Guangzhou , China
| | - Xiao Han
- a Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology , Sun Yat-Sen University , Guangzhou , China
| | - Wenyong Huang
- a Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology , Sun Yat-Sen University , Guangzhou , China
| |
Collapse
|
31
|
Olioso D, Marzotto M, Bonafini C, Brizzi M, Bellavite P. Arnica montana effects on gene expression in a human macrophage cell line. Evaluation by quantitative Real-Time PCR. HOMEOPATHY 2016; 105:131-47. [PMID: 27211321 DOI: 10.1016/j.homp.2016.02.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Revised: 01/01/2016] [Accepted: 02/01/2016] [Indexed: 12/14/2022]
Abstract
BACKGROUND Arnica montana is a popular traditional remedy widely used in complementary medicine, also for its wound healing properties. Despite its acknowledged action in clinical settings at various doses, the molecular aspects relating to how A. montana promotes wound healing remain to be elucidated. To fill this gap, we evaluated the whole plant extract, in a wide range of dilutions, in THP-1 human cells, differentiated into mature macrophages and into an alternative IL-4-activated phenotype involved in tissue remodelling and healing. METHODS Real-time quantitative Reverse Transcription Polymerase Chain Reaction (PCR) analysis was used to study the changes in the expression of a customized panel of key genes, mainly cytokines, receptors and transcription factors. RESULTS On macrophages differentiated towards the wound healing phenotype, A. montana affected the expression of several genes. In particular CXC chemokine ligand 1 (CXCL1), coding for an chief chemokine, exhibited the most consistent increase of expression, while also CXC chemokine ligand 2 (CXCL2), Interleukin8 (IL8) and bone morphogenetic protein (BMP2) were slightly up-regulated, suggesting a positive influence of A. montana on neutrophil recruitment and on angiogenesis. MMP1, coding for a metalloproteinase capable of cleaving extracellular matrix substrates, was down-regulated. Most results showed non-linearity of the dose-effect relationship. CONCLUSIONS This exploratory study provides new insights into the cellular and molecular mechanisms of action of A. montana as a promoter of healing, since some of the genes it modifies are key regulators of tissue remodelling, inflammation and chemotaxis.
Collapse
Affiliation(s)
- Debora Olioso
- Department of Medicine, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy
| | - Marta Marzotto
- Department of Medicine, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy
| | - Clara Bonafini
- Department of Medicine, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy
| | - Maurizio Brizzi
- Department of Statistical Sciences, University of Bologna, Via delle Belle Arti 41, 40126 Bologna, Italy
| | - Paolo Bellavite
- Department of Medicine, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
| |
Collapse
|
32
|
Helling AL, Tsekoura EK, Biggs M, Bayon Y, Pandit A, Zeugolis DI. In Vitro Enzymatic Degradation of Tissue Grafts and Collagen Biomaterials by Matrix Metalloproteinases: Improving the Collagenase Assay. ACS Biomater Sci Eng 2016; 3:1922-1932. [PMID: 33440550 DOI: 10.1021/acsbiomaterials.5b00563] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Matrix metalloproteinase-1 and -8 are active during the wound healing and remodelling processes, degrading native extracellular matrix and implantable devices. However, traditional in vitro assays utilize primarily matrix metalloproteinase-1 to mimic the in vivo degradation microenvironment. Herein, we assessed the influence of various concentrations of matrix metalloproteinase- 1 and 8 (50, 100, and 200 U/mL) as a function of pH (5.5 and 7.4) and time (3, 6, 9, 12, and 24 h) on the degradation profile of three tissue grafts (chemically cross-linked Permacol, nonchemically cross-linked Permacol and nonchemically cross-linked Strattice) and a collagen biomaterial (nonchemically cross-linked collagen sponge). Chemically cross-linked and nonchemically cross-linked Permacol samples exhibited the highest resistance to enzymatic degradation, while nonchemically cross-linked collagen sponges exhibited the least resistance to enzymatic degradation. Qualitative and quantitative degradation analysis of all samples revealed a similar degradation profile over time, independently of the matrix metalloproteinase used and its respective concentration and pH. These data indicate that matrix metalloproteinase-1 and matrix metalloproteinase-8 exhibit similar degradation profile in vitro, suggesting that matrix metalloproteinase-8 should be used for collagenase assay.
Collapse
Affiliation(s)
| | | | | | - Y Bayon
- Sofradim Production, A Medtronic Company, Trévoux, France
| | | | | |
Collapse
|
33
|
Zhang H, Liu B, Xu XF, Jiang TT, Zhang XQ, Shi YL, Chen Y, Liu F, Gu J, Zhu LJ, Wu N. Pathophysiology of chronic pancreatitis induced by dibutyltin dichloride joint ethanol in mice. World J Gastroenterol 2016; 22:2960-2970. [PMID: 26973392 PMCID: PMC4779919 DOI: 10.3748/wjg.v22.i10.2960] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Revised: 08/12/2015] [Accepted: 11/13/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To search for a new chronic pancreatitis model in mice suitable for investigating the pathophysiological processes leading to pancreatic fibrosis. METHODS The mice were randomly divided into 2 groups (n = 50), control group and model group. The mice in model group were given ethanol (10%) in drinking water after injection of dibutyltin dichloride (DBTC) (8 mg/kg BW) in tail vein. The mice in control group were injected with only solvent into tail vein (60% ethanol, 20% glycerine and 20% normal saline) and drank common water. At days 1, 7, 14, 28, and 56 after application of DBTC or solvent, 10 mice in one group were killed at each time point respectively. Blood was obtained by inferior vena cava puncture. The activity of amylase, concentration of bilirubin and hyaluronic acid in serum were assayed. The pancreas was taken to observe the pancreatic morphology by HE staining, and to characterize the pancreatic fibrosis by Masson staining. The expression of F4/80, CD3 and fibronectin (FN) were assayed by immuno-histochemistry or Immunofluorescence technique. Collagen type I (COL1A1) in pancreas were detected by Western blot. The expression of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA in the pancreas was assessed by real time PCR. RESULTS DBTC induced an acute edematous pancreatitis within 1 d. The dilated acini, scattered acinar cell necrosis, and inflammatory cells were found at day 7. Extensive infiltration with inflammatory cells following deposition of connective tissue was observed at day 14. At day 28, level of pancreatic fibrosis was aggravated. The pancreatic tissue was replaced by an extended interstitial fibrosis at the end of 2 mo. There was significant difference in the level of amylase, bilirubin and hyaluronic acid in serum between control group and model group (P < 0.05). The level of COL1A1 and FN in pancreas increased. The expression of MMP-1 mRNA in pancreas decreased, but TIMP-1 mRNA increased at model group. CONCLUSION DBTC joint Ethanol drinking can induce chronic pancreatitis in accordance with the pathophysiological modification of human. DBTC joint Ethanol-induced pancreatitis in mice is an effective and handy experimental method. The model is suitable to study the mechanism of pancreatic fibrosis in chronic pancreatitis.
Collapse
|
34
|
Sundar SS, Jayesh SR, Hussain S. Association of matrix metalloproteinase 1 gene promoter mutation and residual ridge resorption in edentulous patients of South Indian origin. J Pharm Bioallied Sci 2015; 7:S652-5. [PMID: 26538937 PMCID: PMC4606679 DOI: 10.4103/0975-7406.163591] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Background: Matrix metalloproteinase (MMP) are involved in bone transformation at the extraction site postdental extraction. We examined the genetic association between single nucleotide polymorphisms of MMP-1 and continuous atrophy of edentulous mandible. Methods: Buccal cells from 33 edentulous patients were collected using sterile wooden spatula and were suspended in 15 ml falcon tubes containing 1.5 ml of cell lysis buffer, without proteinase K. The cells were transported to the laboratory on ice and were stored at −20°C until being processed. Results: Of the samples analyzed, 26 edentulous patients (78.8%) carried 2G allele, while 7 of them (21.2%) carried 1G allele. Conclusion: The patients with the alveolar bone resorption exhibited more of 2G allele while only 21.2% of them showed 1G allele, associated with excessive atrophy of edentulous mandible. This study may provide genetic background to identify susceptible individuals prone to develop jawbone atrophy after dental extraction.
Collapse
Affiliation(s)
- S Shyam Sundar
- Department of Prosthodontics, Meenakshi Ammal Dental College, Chennai, Tamil Nadu, India
| | - S Ragavendar Jayesh
- Department of prosthodontics, Sree Balaji Dental College and Hospital, Chennai, Tamil Nadu, India
| | - Sharmila Hussain
- Department of Prosthodontics, Madha Dental College, Chennai, Tamil Nadu, India
| |
Collapse
|
35
|
Deschner J, Eick S, Damanaki A, Nokhbehsaim M. The role of adipokines in periodontal infection and healing. Mol Oral Microbiol 2014; 29:258-69. [PMID: 25052571 DOI: 10.1111/omi.12070] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/16/2014] [Indexed: 11/27/2022]
Abstract
Periodontitis is a chronic inflammatory disease of the periodontium, which is caused by pathogenic bacteria in combination with other risk factors. The bacteria induce an immunoinflammatory host response, which can lead to irreversible matrix degradation and bone resorption. Periodontitis can be successfully treated. To achieve regenerative periodontal healing, bioactive molecules, such as enamel matrix derivative (EMD), are applied during periodontal surgery. Recently, it has been shown that obesity is associated with periodontitis and compromised healing after periodontal therapy. The mechanisms underlying these associations are not well understood so far, but adipokines may be a pathomechanistic link. Adipokines are bioactive molecules that are secreted by the adipose tissue, and that regulate insulin sensitivity and energy expenditure, but also inflammatory and healing processes. It has also been demonstrated that visfatin and leptin increase the synthesis of proinflammatory and proteolytic molecules, whereas adiponectin downregulates the production of such mediators in periodontal cells. In addition, visfatin and leptin counteract the beneficial effects of EMD, whereas adiponectin enhances the actions of EMD on periodontal cells. Since visfatin and leptin levels are increased and adiponectin levels are reduced in obesity, these adipokines could be a pathomechanistic link whereby obesity and obesity-related diseases enhance the risk for periodontitis and compromised periodontal healing. Recent studies have also revealed that adipokines, such as visfatin, leptin and adiponectin, are produced in periodontal cells and regulated by periodontopathogenic bacteria. Therefore, adipokines may also represent a mechanism whereby periodontal infections can impact on systemic diseases.
Collapse
Affiliation(s)
- J Deschner
- Experimental Dento-Maxillo-Facial Medicine, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany; Clinical Research Unit 208, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany
| | | | | | | |
Collapse
|
36
|
Lepetsos P, Pampanos A, Kanavakis E, Tzetis M, Korres D, Papavassiliou AG, Efstathopoulos N. Association of MMP-1 -1607 1G/2G (rs1799750) polymorphism with primary knee osteoarthritis in the Greek population. J Orthop Res 2014; 32:1155-60. [PMID: 24838892 DOI: 10.1002/jor.22647] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2014] [Accepted: 04/24/2014] [Indexed: 02/04/2023]
Abstract
Osteoarthritis is the most common form of arthritis with still unknown pathogenic etiology and considerable contribution of genetic factors. One of the mechanisms of cartilage degradation in osteoarthritis is enzymatic proteolysis of the extracellular matrix by metalloproteinases. MMP-1, produced by chondrocytes and synovial cells, is a major proteinase of the MMPs family. The present study aims at evaluating the association of MMP1 gene -1607 1G/2G (rs1799750) polymorphism with primary knee osteoarthritis in the Greek population. One hundred fifty five patients with primary symptomatic knee osteoarthritis participated in the study along with 139 controls. Genotypes were determined using PCR-RLFP technique. Allelic and genotypic frequencies were compared between both study groups. There was no significant association between MMP1 -1607 1G/2G polymorphism and knee osteoarthritis, in crude analysis; however, after multiple logistic regression analysis, 1G/2G was associated with reduced odds of knee osteoarthritis by 75% in males, compared to genotypes 1G/1G + 2G/2G, adjusting for age and BMI (adjusted OR: 0.25, 95% CI: 0.069, 0.910, p = 0.035). The present study shows that MMP1 -1607 1G/2G (rs1799750) polymorphism might be a risk factor for knee osteoarthritis susceptibility in the Greek population. Further investigations are needed to confirm this association in the pathogenesis of osteoarthritis.
Collapse
Affiliation(s)
- Panagiotis Lepetsos
- 2nd Department of Trauma and Orthopaedics, University of Athens Medical School, "Agia Olga" Hospital, 3-5 Ag. Olgas Street, 14233, Nea Ionia, Athens, Greece; Department of Medical Genetics, University of Athens Medical School, "Agia Sophia" Children's Hospital, Thivon and Levadias Str., 11527, Athens, Greece
| | | | | | | | | | | | | |
Collapse
|
37
|
Mete O, Hayhurst C, Alahmadi H, Monsalves E, Gucer H, Gentili F, Ezzat S, Asa SL, Zadeh G. The role of mediators of cell invasiveness, motility, and migration in the pathogenesis of silent corticotroph adenomas. Endocr Pathol 2013; 24:191-8. [PMID: 24091601 DOI: 10.1007/s12022-013-9270-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Silent corticotroph adenomas (SCAs) represent a distinct subset of clinically non-functioning pituitary adenomas. There are two variants of SCA; type I are densely granulated basophilic tumors and type II are sparsely granulated and chromophobic tumors. SCAs are known to be aggressive than the more common non-functioning gonadotroph adenomas (NFGAs). Cell-matrix interactions play an important role in the pathogenesis of pituitary adenomas. In this study, we compared 19 SCAs and 50 NFGAs with known fibroblast growth factor receptor-4 (FGFR4) status using semi-quantitative immunohistochemistry to localize β1-integrin, osteopontin, and matrix metalloproteinase-1 (MMP-1) as cytoplasmic, membranous, or mixed cytoplasmic-membranous staining to achieve scores of 1-4. Staining for β1-integrin was significantly higher in SCAs (100 %, score 3.3) than in NFGAs (96 %; score 2.6) (p = 0.0482); there was no statistical difference within subgroups of SCA (type II score 3.4; type I score 2.8) (p = 0.2663). Osteopontin immunoreactivity was also higher in SCAs (100 %, score 3.7) than in NFGAs (42 %, score 0.8) (p = 0.0001); there was no statistical difference within subgroups of SCA (type II score 3.6; type I score 3.9) (p = 0.2787). In contrast, MMP-1 immunoreactivity was lower in SCAs (89 %; score 2.5) than in NFGAs (98 %; score 3.6) (p = 0.0005); there was no statistical difference within subgroups of SCA (type II score 2.7; type I score 2.0) (p = 0.30704). The MMP-1 results correlated with FGFR4 expression (NFGA 96 %, type II SCA 71 %, type I SCA 40 %). Our data indicate that the biological aggressivity of SCAs compared with NFGA may be due to high osteopontin expression; in contrast, high MMP-1 is characteristic of NFGAs that also express more FGFR4. Further investigations are warranted to clarify the underlying regulatory mechanisms of these markers. The high osteopontin or FGFR4/MMP-1 expression levels in SCAs and NFGAs, respectively, indicate the potential for therapeutic strategies targeting osteopontin or FGFR4/MMP-1 for inoperable tumors of these types.
Collapse
Affiliation(s)
- Ozgur Mete
- Department of Pathology, University Health Network, 200 Elizabeth Street, 11th floor, Toronto, ON, M5G 2C4, Canada,
| | | | | | | | | | | | | | | | | |
Collapse
|
38
|
Stimulation of MMP-1 and CCL2 by NAMPT in PDL cells. Mediators Inflamm 2013; 2013:437123. [PMID: 24058270 PMCID: PMC3766615 DOI: 10.1155/2013/437123] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2013] [Accepted: 07/18/2013] [Indexed: 01/04/2023] Open
Abstract
Periodontitis is an inflammatory disease caused by pathogenic microorganisms and characterized by the destruction of the periodontium. Obese individuals have an increased risk of periodontitis, and elevated circulating levels of adipokines, such as nicotinamide phosphoribosyltransferase (NAMPT), may be a pathomechanistic link between both diseases. The aim of this in vitro study was to examine the regulation of periodontal ligament (PDL) cells by NAMPT and its production under inflammatory and infectious conditions. NAMPT caused a significant upregulation of 9 genes and downregulation of 3 genes, as analyzed by microarray analysis. Eight of these genes could be confirmed by real-time PCR: NAMPT induced a significant upregulation of EGR1, MMP-1, SYT7, ITPKA, CCL2, NTM, IGF2BP3, and NRP1. NAMPT also increased significantly the MMP-1 and CCL2 protein synthesis. NAMPT was significantly induced by interleukin-1β and the periodontal microorganism P. gingivalis. NAMPT may contribute to periodontitis through upregulation of MMP-1 and CCL2 in PDL cells. Increased NAMPT levels, as found in obesity, may therefore represent a mechanism whereby obesity could confer an increased risk of periodontitis. Furthermore, microbial and inflammatory signals may enhance the NAMPT synthesis in PDL cells and thereby contribute to the increased gingival and serum levels of this adipokine, as found in periodontitis.
Collapse
|
39
|
Gupta V, Singh MK, Garg RK, Pant KK, Khattri S. Evaluation of peripheral matrix metalloproteinase-1 in Parkinson's disease: a case-control study. Int J Neurosci 2013; 124:88-92. [PMID: 23849018 DOI: 10.3109/00207454.2013.824438] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Several types of proteinases are implicated in extracellular matrix (ECM) degradation, but the major enzymes are considered to be matrix metalloproteinases (MMPs). Matrix metalloproteinase-1 (MMP-1) is a major proteinase of the MMP family. MMP-1 is critical for modeling and remodeling of the extracellular matrix. In the present study, we evaluated circulating level of MMP-1 in Parkinson's disease (PD) patients and controls. METHOD Enzyme linked immunosorbent assay (ELISA) was used to determine the serum level of MMP-1 in Parkinson's patients and matched healthy controls. RESULTS The mean age of Parkinson's patients (65%) and controls (62.5%) were 55.80 ± 9.69 and 54.05 ± 8.71 years respectively, with similar male/female ratio between patients and controls. The MMP-1 level was (p = 0.005) significantly lower in Parkinson's patients (2380.32 ± 2245.27 pg/ml) as compared to controls (4453.07 ± 3321.01 pg/ml). Poor correlation was found between MMP-1 level and disease duration (r = 0.36, p = 0.02), however it was statistically significant. CONCLUSION Significantly lower level of serum MMP-1 was found in PD patients in comparison to controls. This difference in MMP-1 level was more prominent in females.
Collapse
Affiliation(s)
- Vineeta Gupta
- 1Department of Pharmacology & Therapeutics, King George's Medical University , Lucknow, Uttar Pradesh , India
| | | | | | | | | |
Collapse
|
40
|
Sri Manjari K, Nallari P, Balakrishna N, Vidyasagar A, Prabhakar B, Jyothy A, Venkateshwari A. Influence of matrix metalloproteinase-1 gene -1607 (1G/2G) (rs1799750) promoter polymorphism on circulating levels of MMP-1 in chronic pancreatitis. Biochem Genet 2013; 51:644-54. [PMID: 23644943 DOI: 10.1007/s10528-013-9594-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2012] [Accepted: 11/15/2012] [Indexed: 12/26/2022]
Abstract
This study investigated the role of -1607 (1G/2G) (rs1799750) polymorphism of the MMP-1 gene in chronic pancreatitis. We genotyped 100 patients with chronic pancreatitis and 100 control subjects using tetra-primer ARMS-PCR followed by agarose gel electrophoresis. Serum levels of MMP-1 were determined by Elisa. Statistical analysis was applied to test the significance of the results. The genotypic and allelic distribution varied significantly between the disease group and the control subjects [OD = 1.981 (1.236-3.181), p = 0.004]. MMP-1 levels were higher in subjects homozygous for the 2G allele than in subjects with the 1G allele. The present study revealed a significant association of the MMP-1 -1607 1G/2G (rs1799750) gene promoter polymorphism with chronic pancreatitis, and it can be considered a biological marker in the etiology of chronic pancreatitis.
Collapse
Affiliation(s)
- K Sri Manjari
- Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad 500 016, India
| | | | | | | | | | | | | |
Collapse
|
41
|
Masuda M, Kai K, Takase Y, Tokunaga O. Pathological features of classical polyarteritis nodosa: analysis of 19 autopsy cases. Pathol Res Pract 2013; 209:161-166. [PMID: 23419691 DOI: 10.1016/j.prp.2013.01.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2012] [Revised: 12/28/2012] [Accepted: 01/04/2013] [Indexed: 02/05/2023]
Abstract
Classical polyarteritis nodosa (cPN) is a rare autoimmune disease featuring systemic inflammation of middle- and small-sized arteries. Because most of autopsy cases underwent clinical treatment, arterial fibrinoid necrosis, which is the most specific finding of cPN, is often obscure. The aim of this study was to seek morphological characteristics of the middle-sized arteries in autopsy cases of cPN, and to identify immunohistochemical markers for the diagnosis of cPN. Nineteen patients who had undergone autopsy with a diagnosis of cPN were enrolled. Twenty-one autopsy cases without cPN were examined as control group. Arterial fibrinoid necrosis in medium-sized arteries was observed in 8/19 autopsy cases. Elastica van Gieson staining showed an increased number of elastic fiber layers (P<0.0001) and greater distances between elastic fiber layers (P<0.0001) in the renal middle-sized arteries of the cPN group. These findings probably reflected the post-inflammatory remodeling process after necrotizing vasculitis. On immunohistochemical examination, the cPN group showed high matrix metalloproteinase-1 and tumor necrosis factor-α expressions and decreased smoothelin expression in the vascular wall compared to the control group. When uncertain or atypical autopsy cases of cPN are examined, these findings can help to make the pathological diagnosis of cPN.
Collapse
Affiliation(s)
- Masanori Masuda
- Department of Pathology and Microbiology, Saga University, Faculty of Medicine, Saga, Japan.
| | | | | | | |
Collapse
|
42
|
Abstract
Pituitary adenomas exhibit a wide range of behaviors. The prediction of aggressive or malignant behavior in pituitary adenomas remains challenging; however, the utility of biomarkers is rapidly evolving. In this review, we discuss potential biomarkers as they relate to aggressive behavior in pituitary adenomas. While detailed histological subtyping remains the best independent predictor of aggressive behavior in the majority of cases, evidence suggests that the additional analyses of FGFR4, MMP, PTTG, Ki-67, p53, and deletions in chromosome 11 may contribute to decisions concerning management of aggressive pituitary adenomas.
Collapse
Affiliation(s)
- Ozgur Mete
- Department of Pathology, University Health Network, 200 Elizabeth Street, 11th Floor, Toronto, Ontario, Canada.
| | | | | |
Collapse
|
43
|
Influence of single nucleotide polymorphisms in the MMP1 promoter region on cutaneous melanoma progression. Melanoma Res 2012; 22:169-75. [PMID: 22198560 DOI: 10.1097/cmr.0b013e32834fc46b] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Recently, we reported on the associations of seven single nucleotide polymorphisms (SNPs) in the promoter region of MMP1 gene with susceptibility to cutaneous melanoma (CM). Considering the reported correlation between MMP1 expression and melanoma progression, we hypothesized that these promoter SNPs might affect CM progression and prognosis. In this study, we examined the associations of seven SNPs with overall survival, as well as six clinicopathological factors in 754 patients with CM. After adjustment for 11 covariates, we observed significant associations of the SNP -422A>T (rs475007) with ulceration status (P=0.012), primary tumor thickness (P=0.040), and anatomic site (P=0.030). We also observed significant associations of the SNP -755T>G (rs498186) with ulceration status (P=0.038) and anatomic site (P=0.003). Two SNPs, -839G>A and -519A>G, were marginally associated with primary tumor thickness, ulceration status, and anatomic site. Furthermore, the frequency of haplotype 2G-G-G-A-A-G-T was higher in patients with ulceration (odds ratio=2.18, 95% confidence interval: 1.08-4.40, P=0.030) compared with those without ulceration. However, we did not find significant associations of these SNPs with overall survival and other clinical factors. As primary tumor thickness and ulceration status are two important indicators of tumor progression and have significant associations with melanoma prognosis, our results suggested that these promoter SNPs in MMP1 might have potential effects on melanoma progression and prognosis by influencing related clinical factors.
Collapse
|
44
|
Romi F, Helgeland G, Gilhus NE. Serum Levels of Matrix Metalloproteinases: Implications in Clinical Neurology. Eur Neurol 2012; 67:121-8. [DOI: 10.1159/000334862] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2011] [Accepted: 11/04/2011] [Indexed: 12/11/2022]
|
45
|
Tewari A, Lahmann C, Sarkany R, Bergemann J, Young AR. Human erythema and matrix metalloproteinase-1 mRNA induction, in vivo, share an action spectrum which suggests common chromophores. Photochem Photobiol Sci 2011; 11:216-23. [PMID: 22080054 DOI: 10.1039/c1pp05243h] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Matrix metalloproteinase 1 (MMP-1) is widely regarded as a biomarker of photoageing. We tested the hypothesis that MMP-1 mRNA expression and erythema share a common action spectrum by comparing the effects of erythemally equivalent doses of UVB, UVA1 and solar simulated radiation (SSR) on acute MMP-1 mRNA expression in whole human skin in vivo. Our results show comparable MMP-1 expression with all three spectra, which supports our hypothesis. The sharing of an action spectrum implies common chromophores, one of which is likely to be DNA. We have previously shown that all spectra that we used readily induce cyclobutane thymine dimers (T<>T) in human epidermis in vivo but we lack quantitative data on damage to dermal DNA. This is important because we do not know if dermal MMP-1 induction occurs via direct damage to the dermis, or indirectly via damage to the epidermis. Our results show that UVB induces about 3 times more T<>T compared with erythemally equivalent doses of UVA1, which is similar to our published epidermal data. This supports previously published work that also implicates an unknown UVA1 chromophore for erythema and MMP-1 induction. However, the distribution of the dermal DNA damage varies considerably with spectrum. In the case of UVB it is primarily in the upper dermis, but with UVA1 it is evenly distributed. Thus, irrespective of chromophores, MMP-1 induction by direct dermal damage by both spectra is possible. The practical conclusions of our data are that the small (<5%) UVB content of solar UVR is likely to be the main cause of photoageing, at least in terms of MMP-1 expression. Furthermore, prevention of erythema by sunscreen use is likely to result in reduced MMP-1 expression.
Collapse
Affiliation(s)
- Angela Tewari
- King's College London (KCL), King's College London School of Medicine, Division of Genetics and Molecular Medicine, St John's Institute of Dermatology, London, UK
| | | | | | | | | |
Collapse
|
46
|
Plasma TGF-β1, MMP-1 and MMP-3 Levels in Chronic Pancreatitis. Indian J Clin Biochem 2011; 27:152-6. [PMID: 23542130 DOI: 10.1007/s12291-011-0167-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2011] [Accepted: 09/12/2011] [Indexed: 01/08/2023]
Abstract
Chronic pancreatitis (CP) presenting clinically with upper abdominal pain, as well as exocrine and endocrine insufficiencies, is characterized by irreversible morphological and functional alterations in the pancreas. The objective of the present study is to investigate the plasma levels of transforming growth factor-β 1 (TGF-β1), matrix metalloproteinases MMP-1 (collagenase) and MMP-3 (stromelysin) in CP. A total of 71 CP patients and 100 control subjects were considered for the study. Plasma levels of TGF-β1, MMP-1 and MMP-3 were determined by enzyme-linked immunosorbent assay in patients and control subjects. The plasma levels of TGF-β1 and MMP-1 were significantly elevated in patients compared to control group (*P = 0.0301, **P < 0.0001). However, there was no significant difference in the plasma levels of MMP-3 between patients and controls (P = 0.3756). The elevated levels of TGF-β1 and MMP-1 may influence the inflammatory reactions by enhancing the pancreatic stellate cell activation and deposition of extracellular matrix resulting in pancreatic fibrosis. Thus, the present study highlights the role of fibrogenic cytokine marker TGF-β1 and matrix metalloproteinases in the pathogenesis of CP.
Collapse
|
47
|
Langers AM, Verspaget HW, Hommes DW, Sier CF. Single-nucleotide polymorphisms of matrix metalloproteinases and their inhibitors in gastrointestinal cancer. World J Gastrointest Oncol 2011; 3:79-98. [PMID: 21731908 PMCID: PMC3124635 DOI: 10.4251/wjgo.v3.i6.79] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2011] [Revised: 05/27/2011] [Accepted: 06/03/2011] [Indexed: 02/05/2023] Open
Abstract
Matrix metalloproteinases (MMPs) are implicated in cancer development and progression and are associated with prognosis. Single-nucleotide polymorphisms (SNPs) of MMPs, most frequently located in the promoter region of the genes, have been shown to influence cancer susceptibility and/or progression. SNPs of MMP-1, -2, -3, -7, -8, -9, -12, -13 and -21 and of the tissue inhibitor of metalloproteinases (TIMPs) TIMP-1 and TIMP-2 have been studied in digestive tract tumors. The contribution of these polymorphisms to the cancer risk and prognosis of gastrointestinal tumors are reviewed in this paper.
Collapse
Affiliation(s)
- Alexandra Mj Langers
- Alexandra MJ Langers, Hein W Verspaget, Daniel W Hommes, Cornelis FM Sier, Department of Gastroenterology and Hepatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
| | | | | | | |
Collapse
|
48
|
Tanindi A, Sahinarslan A, Elbeg S, Cemri M. Relationship Between MMP-1, MMP-9, TIMP-1, IL-6 and Risk Factors, Clinical Presentation, Extent and Severity of Atherosclerotic Coronary Artery Disease. Open Cardiovasc Med J 2011; 5:110-6. [PMID: 21772929 PMCID: PMC3136999 DOI: 10.2174/1874192401105010110] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2011] [Revised: 04/12/2011] [Accepted: 04/14/2011] [Indexed: 02/04/2023] Open
Abstract
Background: Matrix metalloproteinases (MMPs) and Tissue Inhibitor of Matrix Metalloproteinases (TIMPs) may be associated with atherogenesis and plaque rupture. We evaluated the relationship between MMP-1, MMP-9, TIMP-1 and IL-6 levels and risk factors, presentation, extent and severity of atherosclerotic coronary artery disease (CAD). Methods: Consecutive patients who underwent coronary angiography were randomly included. The serum concentrations of MMP-1, MMP-9, TIMP-1 and IL-6 were analyzed with ELISA method in 134 patients. Participants were divided into 5 groups; stable angina pectoris (SAP; n= 34), unstable angina pectoris (USAP; n=29), non-ST elevation myocardial infarction (NSTEMI; n=16), acute ST elevation myocardial infarction (STEMI; n=25) and controls (n=30). Coronary angiographic Gensini score was calculated. Results: MMP-1 levels were higher in STEMI and NSTEMI groups compared with USAP, SAP and control groups (STEMI vs USAP p=0.005; STEMI vs SAP p=0.001; STEMI vs control p<0.001; NSTEMI vs USAP p=0.02; NSTEMI vs SAP p=0.027; NSTEMI vs control p<0.001). In STEMI group, MMP-9 levels were higher than USAP and control groups (p=0.002; p<0,001). TIMP-1 levels were not significantly different within all 5 groups. MMP-1 levels were found to be elevated in diabetic patients (p=0.020); whereas MMP-9 levels were higher in smokers (p=0.043). Higher MMP-1, MMP-9 and IL-6 levels were correlated with severe Left Anterior Descending artery (LAD) stenosis and higher angiographic Gensini Score (for severe LAD stenosis; r = 0.671, 0.363, 0.509 p<0.001; for Gensini score; r = 0.717, 0.371, 0.578 p<0.001). Conclusions: Serum levels of MMP-1, MMP-9, and IL-6 are elevated in patients with CAD; more so in acute coronary syndromes. MMP-1, MMP-9 and IL-6 are associated with more extensive and severe CAD (as represented by Gensini score).
Collapse
Affiliation(s)
- Asli Tanindi
- Gazi University Faculty of Medicine, Department of Cardiology, Turkey
| | | | | | | |
Collapse
|
49
|
Halfon S, Abramov N, Grinblat B, Ginis I. Markers distinguishing mesenchymal stem cells from fibroblasts are downregulated with passaging. Stem Cells Dev 2010; 20:53-66. [PMID: 20528146 DOI: 10.1089/scd.2010.0040] [Citation(s) in RCA: 248] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Expansion of plastic-adherent bone marrow-derived mesenchymal stem cells (MSCs) results in gradual loss of osteogenic potential after passage 5-6. One explanation is contamination of MSC cultures with mature cells including fibroblasts. Identification and elimination of fibroblasts from MSC cultures could improve MSC yield and differentiation potential and also prevent tumor formation after MSC transplantation. However, no specific markers currently exist that can reliably discriminate between MSCs and fibroblasts. Flow cytometry analysis demonstrated that markers currently used to define MSCs, such as CD105, CD166, CD90, CD44, CD29, CD73, and CD9, are also expressed on human skin or lung fibroblasts. However, the level of expression of CD166 was significantly higher and that of CD9 was significantly lower in MSCs than in fibroblasts. CD146 was expressed only in MSCs. Using small focused microarrays, new markers differentially expressed in MSCs and fibroblasts were identified. Real-time polymerase chain reaction confirmed that expression of CD106, integrin alpha 11, and insulin-like growth factor-2 in MSCs was at least 10-fold higher than in fibroblasts; whereas expression of matrix metalloproteinase 1 and matrix metalloproteinase 3 was almost 100-fold lower. Flow cytometry and immunostaining demonstrated that CD106 protein expression on cell surface could be upregulated in MSCs but not in fibroblasts by the treatment with tumor necrosis factor-alpha. Comparison of surface expression of commonly used and newly identified MSC markers in MSCs cultures of passage 2 and passage 6 demonstrated that CD106 (with and without tumor necrosis factor-alpha treatment), integrin alpha 11, and CD146 were downregulated in MSCs of passage 6, and CD9 was upregulated; whereas all other markers did not change. Newly identified markers that have robust differences of expression in MSCs and fibroblasts on gene and protein level could be used for quality control of MSC cultures after expansion, cryopreservation, gene transfection, and other manipulations.
Collapse
|