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Xu Q, Peng A, Zhao L, Wang L. Down-regulated circ_0001853 inhibits lipopolysaccharide-induced endometritis progression via sponging miR-34c-5p. Mol Cell Probes 2025; 81:102023. [PMID: 40058671 DOI: 10.1016/j.mcp.2025.102023] [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: 01/16/2025] [Revised: 03/01/2025] [Accepted: 03/06/2025] [Indexed: 03/18/2025]
Abstract
BACKGROUND To investigate the diagnostic value and mechanism of action of circular RNA (circ_) circ_0001853 and microRNA (miR) miR-34c-5p in patients with endometritis. METHODS 189 patients with endometritis and 176 healthy individuals were included in this study. Venous blood serum was collected from the study subjects and stored temporarily at -80 °C. Real-time quantitative chain polymerase reaction (RT-qPCR) was used to detect circ_0001853 and miR-34c-5p expression, and receiver operating characteristic (ROC) curves assessed the diagnostic value of both in predicting endometritis. Cell counting kit (CCK8) observed cell proliferation, flow cytometry recorded apoptosis, enzyme linked immunosorbent assay (ELISA) monitored inflammatory factor expression, and dual luciferase reporter assay and RNA immunoprecipitation (RIP) verified the relationship between circ_0001853 and miR-34c-5p targeting interactions. RESULTS High levels of circ_0001853 and low levels of miR-34c-5p were present in endometritis patients, and they were negatively correlated. Both circ_0001853 and miR-34c-5p alone or in combination had diagnostic value in predicting the progression of endometritis. Transfection of si-circ_0001853 promoted cell proliferation and reduced apoptosis and cellular inflammation levels induced by lipopolysaccharide (LPS) stimulation. There was a direct reciprocal targeting relationship between miR-34c-5p and circ_0001853, and the use of miR-34c-5p inhibitor resisted silencing circ_0001853 promoted cell proliferation and increased the number of apoptotic cells and cellular inflammation levels. CONCLUSIONS circ_0001853 is involved in endometritis progression through miR-34c-5p, i.e., low circ_0001853 promotes miR-34c-5p-induced proliferation of epithelial cells, reduces apoptosis, and suppresses inflammation levels, preventing disease progression.
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Affiliation(s)
- Qian Xu
- Department of Gynaecology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Changde, 415003, China
| | - Ailing Peng
- Department of Gynaecology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Changde, 415003, China
| | - Liyun Zhao
- Department of Gynaecology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Changde, 415003, China
| | - Li Wang
- Department of Gynaecology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Changde, 415003, China.
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Asif S, Gulzar MW. A narrative review on MicroRNA's role in diagnosis and therapy of equine endometritis. J Reprod Immunol 2025; 169:104459. [PMID: 39987676 DOI: 10.1016/j.jri.2025.104459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 02/06/2025] [Accepted: 02/17/2025] [Indexed: 02/25/2025]
Abstract
Endometritis is a significant cause of infertility in mare. Some infectious agents disrupt the endometrium's innate immune system, resulting in a prolonged systemic inflammatory response that circulates via the blood or cellular degeneration, which ultimately leads to endometritis from bacterial endotoxins. Numerous biological processes use various small, non-coding RNA molecules called MicroRNAs. MicroRNAs (miRNAs) regulate gene expression after transcription by blocking transcription and translation. This manuscript examines patho-morphological discoveries in equine endometritis, the expression and effects of eca-miR-17, eca-miR-223, eca-miR-200a, eca-miR-155, and eca-miR-205, and the therapeutic function of miRNA in endometritis. MiRNAs play a crucial role in controlling inflammatory disorders by modulating cytokine signaling pathways. This review emphasizes the demand for cutting-edge genetic technologies and the development of novel pharmaceutical preparations to improve our understanding of the genes encoding by these miRNAs. It also focuses on the efficacy of miRNAs for control, early diagnosis, and prevention of endometritis.
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Affiliation(s)
- Sana Asif
- Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China
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3
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Wang S, Liu R, Ren X, Sang M, Dong H, Wu Q, Li A. The bta-miR-22-3p can alleviate LPS-induced inflammatory response in yak endometrial epithelial cells by targeting KSR2. Microb Pathog 2024; 197:107090. [PMID: 39510361 DOI: 10.1016/j.micpath.2024.107090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 10/23/2024] [Accepted: 10/28/2024] [Indexed: 11/15/2024]
Abstract
Bovine endometritis is a common reproductive system disease in dairy cows that leads to decreased milk production and reproductive performance, causing significant economic losses for farmers. Research has shown that microRNAs (miRNAs) play a significant role in regulating the expression of biological genes and are closely related to the occurrence of inflammation, including bta-miR-22-3p. However, the specific molecular mechanisms by which miRNAs regulate bovine endometritis remain unclear. To investigate the regulatory mechanism of bta-miR-22-3p in yak endometritis, uterine tissues were collected from three healthy bos grunniens and three bos grunniens with endometritis, approximately 21 days postpartum. Various methods were employed, including real-time quantitative polymerase chain reaction (RT-qPCR), Western blot (WB), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence (IF). The results demonstrated that overexpression of bta-miR-22-3p led to a significant decrease (P < 0.05) in factors related to the mitogen-activated protein kinase (MAPK) signaling pathway and associated inflammatory factors, such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (P38), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Furthermore, dual-luciferase assays confirmed that the kinase suppressor of the Ras 2 (KSR2) gene is a downstream target of bta-miR-22-3p. Overexpression of bta-miR-22-3p inhibited the expression of KSR2. When KSR2 was inhibited, the levels of MAPK signaling pathway-related factors and inflammation also significantly decreased (P < 0.05). Thus, bta-miR-22-3p suppresses the activation of the MAPK signaling pathway through the inhibition of KSR2, resulting in a reduction of inflammatory factors. In conclusion, this study demonstrated that bta-miR-22-3p targets the KSR2 gene to alleviate LPS (Lipopolysaccharide)-induced inflammatory damage.
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Affiliation(s)
- Shuo Wang
- Key Laboratory of Clinical Veterinary Medicine, Animal Science College, Xizang Agriculture and Animal Husbandry University, Linzhi, 860000, China
| | - Ruidong Liu
- Key Laboratory of Clinical Veterinary Medicine, Animal Science College, Xizang Agriculture and Animal Husbandry University, Linzhi, 860000, China
| | - Xiaoli Ren
- Key Laboratory of Clinical Veterinary Medicine, Animal Science College, Xizang Agriculture and Animal Husbandry University, Linzhi, 860000, China
| | - Mudan Sang
- Key Laboratory of Clinical Veterinary Medicine, Animal Science College, Xizang Agriculture and Animal Husbandry University, Linzhi, 860000, China
| | - Hailong Dong
- Key Laboratory of Clinical Veterinary Medicine, Animal Science College, Xizang Agriculture and Animal Husbandry University, Linzhi, 860000, China.
| | - Qingxia Wu
- Key Laboratory of Clinical Veterinary Medicine, Animal Science College, Xizang Agriculture and Animal Husbandry University, Linzhi, 860000, China
| | - Aoyun Li
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, China.
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Rodríguez-Eguren A, Bueno-Fernandez C, Gómez-Álvarez M, Francés-Herrero E, Pellicer A, Bellver J, Seli E, Cervelló I. Evolution of biotechnological advances and regenerative therapies for endometrial disorders: a systematic review. Hum Reprod Update 2024; 30:584-613. [PMID: 38796750 PMCID: PMC11369227 DOI: 10.1093/humupd/dmae013] [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: 12/07/2023] [Revised: 04/12/2024] [Indexed: 05/28/2024] Open
Abstract
BACKGROUND The establishment and maintenance of pregnancy depend on endometrial competence. Asherman syndrome (AS) and intrauterine adhesions (IUA), or endometrial atrophy (EA) and thin endometrium (TE), can either originate autonomously or arise as a result from conditions (i.e. endometritis or congenital hypoplasia), or medical interventions (e.g. surgeries, hormonal therapies, uterine curettage or radiotherapy). Affected patients may present an altered or inadequate endometrial lining that hinders embryo implantation and increases the risk of poor pregnancy outcomes and miscarriage. In humans, AS/IUA and EA/TE are mainly treated with surgeries or pharmacotherapy, however the reported efficacy of these therapeutic approaches remains unclear. Thus, novel regenerative techniques utilizing stem cells, growth factors, or tissue engineering have emerged to improve reproductive outcomes. OBJECTIVE AND RATIONALE This review comprehensively summarizes the methodologies and outcomes of emerging biotechnologies (cellular, acellular, and bioengineering approaches) to treat human endometrial pathologies. Regenerative therapies derived from human tissues or blood which were studied in preclinical models (in vitro and in vivo) and clinical trials are discussed. SEARCH METHODS A systematic search of full-text articles available in PubMed and Embase was conducted to identify original peer-reviewed studies published in English between January 2000 and September 2023. The search terms included: human, uterus, endometrium, Asherman syndrome, intrauterine adhesions, endometrial atrophy, thin endometrium, endometritis, congenital hypoplasia, curettage, radiotherapy, regenerative therapy, bioengineering, stem cells, vesicles, platelet-rich plasma, biomaterials, microfluidic, bioprinting, organoids, hydrogel, scaffold, sheet, miRNA, sildenafil, nitroglycerine, aspirin, growth hormone, progesterone, and estrogen. Preclinical and clinical studies on cellular, acellular, and bioengineering strategies to repair or regenerate the human endometrium were included. Additional studies were identified through manual searches. OUTCOMES From a total of 4366 records identified, 164 studies (3.8%) were included for systematic review. Due to heterogeneity in the study design and measured outcome parameters in both preclinical and clinical studies, the findings were evaluated qualitatively and quantitatively without meta-analysis. Groups using stem cell-based treatments for endometrial pathologies commonly employed mesenchymal stem cells (MSCs) derived from the human bone marrow or umbilical cord. Alternatively, acellular therapies based on platelet-rich plasma (PRP) or extracellular vesicles are gaining popularity. These are accompanied by the emergence of bioengineering strategies based on extracellular matrix (ECM)-derived hydrogels or synthetic biosimilars that sustain local delivery of cells and growth factors, reporting promising results. Combined therapies that target multiple aspects of tissue repair and regeneration remain in preclinical testing but have shown translational value. This review highlights the myriad of therapeutic material sources, administration methods, and carriers that have been tested. WIDER IMPLICATIONS Therapies that promote endometrial proliferation, vascular development, and tissue repair may help restore endometrial function and, ultimately, fertility. Based on the existing evidence, cost, accessibility, and availability of the therapies, we propose the development of triple-hit regenerative strategies, potentially combining high-yield MSCs (e.g. from bone marrow or umbilical cord) with acellular treatments (PRP), possibly integrated in ECM hydrogels. Advances in biotechnologies together with insights from preclinical models will pave the way for developing personalized treatment regimens for patients with infertility-causing endometrial disorders such as AS/IUA, EA/TE, and endometritis. REGISTRATION NUMBER https://osf.io/th8yf/.
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Affiliation(s)
- Adolfo Rodríguez-Eguren
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA
| | - Clara Bueno-Fernandez
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain
- Department of Paediatrics, Obstetrics and Gynecology, Faculty of Medicine, University of Valencia, Valencia, Spain
| | - María Gómez-Álvarez
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain
| | - Emilio Francés-Herrero
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain
- Department of Paediatrics, Obstetrics and Gynecology, Faculty of Medicine, University of Valencia, Valencia, Spain
| | - Antonio Pellicer
- Department of Paediatrics, Obstetrics and Gynecology, Faculty of Medicine, University of Valencia, Valencia, Spain
- IVIRMA Global Research Alliance, IVI Rome, Rome, Italy
| | - José Bellver
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain
- Department of Paediatrics, Obstetrics and Gynecology, Faculty of Medicine, University of Valencia, Valencia, Spain
- IVIRMA Global Research Alliance, IVI Valencia, Valencia, Spain
| | - Emre Seli
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA
- IVIRMA Global Research Alliance, IVIRMA New Jersey, Basking Ridge, NJ, USA
| | - Irene Cervelló
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain
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Chen Y, Zheng S, Zhao X, Zhang Y, Yu S, Wei J. Unveiling the protective effects of BMSCs/anti-miR-124-3p exosomes on LPS-induced endometrial injury. Funct Integr Genomics 2024; 24:32. [PMID: 38363406 DOI: 10.1007/s10142-024-01303-4] [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: 09/30/2023] [Revised: 01/15/2024] [Accepted: 01/17/2024] [Indexed: 02/17/2024]
Abstract
Researchers have reported that miR-124-3p is highly expressed in patients with chronic endometritis. However, the underlying mechanism of miR-124-3p in the development of endometritis remains unclear. This study constructed an in vitro endometrial cell injury model by treating HEECs with 2 μg/mL LPS for 48 h. Then, 1 mg/kg LPS was injected into both sides of the mouse uterus to construct an in vivo endometrial injury model. The expression of miR-124-3p in human endometrial epithelial cells (HEECs) was assessed using RT‒qPCR. Exosomes were separated from bone marrow-derived mesenchymal stem cells (BMSCs) and cocultured with HEECs. A dual-luciferase reporter assay was performed to confirm the relationship between miR-124-3p and DUSP6. The results indicated that LPS inhibited HEEC viability in a time- and dose-dependent manner. The miR-124-3p inhibitor reversed the LPS-induced apoptosis and inhibition of HEEC viability. In addition, miR-124-3p could be transferred from BMSCs to HEECs by exosomes. Exosomes were derived from BMSCs treated with an NC inhibitor (BMSCs/NC Exo) or miR-124-3p inhibitor (BMSCs/anti-miR-124-3p Exo). In addition, BMSCs/anti-miR-124-3p Exo abolished the LPS-induced inhibition of HEEC viability and proliferation by inducing HEEC apoptosis. Moreover, BMSCs/anti-miR-124-3p Exo alleviated the LPS-induced inflammation of HEECs by upregulating DUSP6 and downregulating p-p65 and p-ERK. Furthermore, in an LPS-induced in vivo endometrial injury model, BMSCs/anti-miR-124-3p Exo increased the expression level of DUSP6 and decreased the expression levels of p-p65 and p-ERK. BMSCs/anti-miR-124-3p Exo protected against LPS-induced endometrial damage in vitro and in vivo by upregulating DUSP6 and downregulating p-p65 and p-ERK1/2. This study showed that BMSCs/anti-miR-124-3p Exo might be a potential alternative for the treatment of endometritis.
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Grants
- 2020J01986, 2021J1236, 2022J01689 Natural Science Foundation of Fujian Province
- 2020J01986, 2021J1236, 2022J01689 Natural Science Foundation of Fujian Province
- 2020J01986, 2021J1236, 2022J01689 Natural Science Foundation of Fujian Province
- 2020J01986, 2021J1236, 2022J01689 Natural Science Foundation of Fujian Province
- 2020J01986, 2021J1236, 2022J01689 Natural Science Foundation of Fujian Province
- 2020J01986, 2021J1236, 2022J01689 Natural Science Foundation of Fujian Province
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Affiliation(s)
- Yihong Chen
- Department of Obstetrics and Gynecology, the First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China
| | - Shan Zheng
- Department of Obstetrics and Gynecology, the First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China
| | - Xiumei Zhao
- Department of Obstetrics and Gynecology, the First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China
| | - Yi Zhang
- Department of Obstetrics and Gynecology, the First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China
| | - Suchai Yu
- Department of Obstetrics and Gynecology, the First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China
| | - Juanbing Wei
- Department of Obstetrics and Gynecology, the First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian, China.
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Asif S, Umar T, Umar Z, Jamil H, Feng H, Zhang P, Umer S. MicroRNAs in equine Endometritis: A review of pathophysiology and molecular insights for diagnostic and therapeutic strategies. Int Immunopharmacol 2023; 124:110949. [PMID: 37725848 DOI: 10.1016/j.intimp.2023.110949] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 09/12/2023] [Accepted: 09/13/2023] [Indexed: 09/21/2023]
Abstract
Endometritis plays an important role in mare infertility. Certain infectious agents interfere with the innate immune system of endometrium, causing a systemic inflammatory response that lasts for a long time and circulates via the blood or cellular degeneration, leading to endometritis due to bacterial endotoxins. Different small, non-coding RNA molecules are involved in many biological functions. For instance, microRNAs (miRNAs) are involved in the post-transcriptional regulation of gene expression. These miRNAs are important regulators of gene expression, primarily via inhibiting transcription and translation processes. This manuscript reviews: (1) pathomorphological findings in equine endometritis, (2) the expression and effects of eca-miR-17, eca-miR-223, eca-miR-200a, eca-miR-155, and eca-miR-205 in endometritis and (3) the therapeutic role of miRNA in equine endometritis. The miRNAs have a vital regulatory role in a wide range of inflammatory diseases by regulating the molecular mechanism of cytokines that cause inflammation through signal pathways. This review emphasizes the demand for cutting-edge genetic technologies and the development of novel pharmaceutical preparations to improve our understanding of the genes encoding by these miRNAs. It also focuses on the efficacy of miRNAs for control, early diagnosis, and prevention of endometritis.
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Affiliation(s)
- Sana Asif
- Department of Theriogenology, University of Agriculture, Faisalabad, 38000 Punjab, Pakistan
| | - Talha Umar
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
| | - Zaima Umar
- Department of Anatomy, The University of Faisalabad, Faisalabad, 38000 Punjab, Pakistan
| | - Huma Jamil
- Department of Theriogenology, University of Agriculture, Faisalabad, 38000 Punjab, Pakistan
| | - Huili Feng
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; College of Animal Husbandry Engineering, Henan Vocational College of Agriculture, Zhengzhou City 451450, China
| | - Peipei Zhang
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Haidian District, Beijing 100193, China
| | - Saqib Umer
- Department of Theriogenology, University of Agriculture, Faisalabad, 38000 Punjab, Pakistan.
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Qian X, Wang Y, Li X, Li Y, Li L. TNFAIP3 interacting protein 2 relieves lipopolysaccharide (LPS)-induced inflammatory injury in endometritis by inhibiting NF-kappaB activation. Immun Inflamm Dis 2023; 11:e970. [PMID: 37904691 PMCID: PMC10571501 DOI: 10.1002/iid3.970] [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: 03/10/2023] [Revised: 07/18/2023] [Accepted: 07/21/2023] [Indexed: 11/01/2023] Open
Abstract
BACKGROUND Endometritis seriously affects the health of women, and it is important to identify new targets for its treatment. OBJECTIVE This study aimed to explore the role of TNFAIP3 interacting protein 2 (TNIP2) in endometritis through human endometrial epithelial cells (hEECs) stimulated by lipopolysaccharide (LPS). METHODS hEECs were induced with LPS to build a cellular model of endometritis. Cell growth and apoptosis were detected by cell counting kit-8 and flow cytometry. The TNIP2 mRNA and protein levels were measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. The caspase3 activity was calculated using a Caspase3 activity kit. Interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels were determined by enzyme-linked-immunosorbent-assay. The reactive oxygen species (ROS), lactate dehydrogenase (LDH), catalase (CAT), and superoxide dismutase (SOD) levels were determined using the corresponding kits. Nuclear factor-kappaB (NF-κB) pathway was determined by western blot assay. RESULTS TNIP2 was downregulated in the LPS-induced endometritis cell model. Cell viability was reduced, apoptosis was enhanced, and IL-6, IL-1β, and TNF-α levels increased in LPS-induced hEECs. Additionally, LDH activity and ROS concentration were upregulated, whereas CAT and SOD activities were downregulated in LPS-induced hEECs. These results were reversed by TNIP2 overexpression. Moreover, the results hinted that NF-κB was involved in the effects of TNIP2 on the LPS-induced endometritis cell model. CONCLUSION TNIP2 alleviated endometritis by inhibiting the NF-κB pathway, suggesting a potential therapeutic target for endometritis.
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Affiliation(s)
- Xinxin Qian
- Department of GynecologyThe Third Affiliated Hospital of Qiqihar Medical CollegeQiqiharChina
| | - Yan Wang
- Department of GynecologyThe Third Affiliated Hospital of Qiqihar Medical CollegeQiqiharChina
| | - Xingmei Li
- Department of GynecologyThe Third Affiliated Hospital of Qiqihar Medical CollegeQiqiharChina
| | - Yuewen Li
- Department of GynecologyThe Third Affiliated Hospital of Qiqihar Medical CollegeQiqiharChina
| | - Liping Li
- Department of GynecologyThe Third Affiliated Hospital of Qiqihar Medical CollegeQiqiharChina
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Taravat M, Asadpour R, Jozani RJ, Fattahi A, Khordadmehr M. Enhanced anti-inflammatory effect of Rosmarinic acid by encapsulation and combination with the exosome in mice with LPS-induced endometritis through suppressing the TLR4-NLRP3 signaling pathway. J Reprod Immunol 2023; 159:103992. [PMID: 37451160 DOI: 10.1016/j.jri.2023.103992] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 05/16/2023] [Accepted: 07/10/2023] [Indexed: 07/18/2023]
Abstract
The TLR4-NLRP3 signaling pathway plays an essential role in the development of inflammation and especially endometritis. Rosmarinic acid (RA) can have potent anti-inflammatory effects in the drug-loading system. The purpose of this was to evaluate the anti-inflammatory effects of RA loaded to exosomes (RLE) on lipopolysaccharide (LPS)-induced endometritis in mice. RA was loaded into serum-derived exosome, using sonication methods. Animals in the treatment groups were subjected to uterine horn injection of RA, exosome, RA combination with exosome (R+E), and RA loaded to exosome (RLE) in uterine horn by two dosages in each group (5 and 10 mg/kg of RA or exosome), 24 h after inducing endometritis. Histopathological analysis, MPO production, immunohistochemistry, and qPCR were used to determine whether the treatment groups were adequate in controlling inflammation. The results showed that treatment groups, and mainly RLE10 and R10 +E10 groups, could modulate pathological changes, inhibit myeloperoxidase (MPO) activity, and significantly reduce the gene and protein expression of TLR4, NLRP3, inflammatory cytokines such as IL-1β, IL-18, and TNF-α, and lastly, GSDM-D as a pyroptosis factor. In conclusion, RA loaded and combination with exosomes at a dosage of 10 mg/kg (RLE10 and R10 +E10) improved endometritis in mice through a suppressing TLR4-NLRP3 signaling pathway.
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Affiliation(s)
- Morteza Taravat
- Department of Clinical Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
| | - Reza Asadpour
- Department of Clinical Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
| | - Razi Jafari Jozani
- Department of Clinical Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
| | - Amir Fattahi
- Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Monireh Khordadmehr
- Department of Basic science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
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Fan L, Wang C, Zhan P, Liu Y. LncRNA RBAT1 reduces chemosensitivity of cancer cells to carboplatin/paclitaxel by sponging miR‑27b in endometrial carcinoma. J Ovarian Res 2023; 16:147. [PMID: 37501162 PMCID: PMC10375650 DOI: 10.1186/s13048-023-01235-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 11/02/2022] [Indexed: 07/29/2023] Open
Abstract
BACKGROUND A recent study reported the role of long non-coding RNA (lncRNA) RBAT1 in promoting the development of retinoblastoma and bladder cancer. However, its function in other cancers is unclear. We then studied the role of RBAT1 in endometrial carcinoma (EC). METHODS The expression of RBAT1 and miR-27b in EC and paired non-tumor samples from advanced EC patients, as well as in plasma samples of EC patients and healthy controls were detected by RT-qPCR. The direct interaction between RBAT1 and miR-27b, and the subcellular location of RBAT1 were determined by RNA-RNA pulldown assay and subcellular fractionation assay, respectively. RESULTS EC tissues showed increased expression levels of RBAT1 and decreased expression levels of miR-27b compared to that in non-tumor tissues. Moreover, EC patients showed higher plasma expression levels of RBAT1 and lower plasma expression levels of miR-27b compared to that in the controls. Drug-resistant (DR) patients showed higher expression levels of RBAT1 and lower expression levels of miR-27b in both EC tissues and plasma samples. RBAT1 was detected in both nuclear and cytoplasm and it directly interacted with miR-27b. RBAT1 and miR-27b did not affect the expression of each other. Upregulation of RBAT1 promoted the expression of multidrug-resistant-related protein (P-gp, MRP1, and BCRP). Overexpression of RBAT1 and inhibition of miR-27b promoted cell viability and impeded cell apoptosis and cell cycle arrest at G0-G1 phase, while knockdown of RBAT1 and overexpression of miR-27b inhibited cell viability and induced cell apoptosis and cell cycle arrest at G0-G1 phase. Moreover, miR-27b could abolish RBAT1-induced effects on cell viability, apoptosis and cell cycle. CONCLUSION RBAT1 may reduce the chemosensitivity of EC cells to carboplatin/paclitaxel by sponging miR-27b in EC.
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Affiliation(s)
- Lingye Fan
- Department of Gynaecology, The Affiliated Hospital of Southwest Medical University, Luzhou City, Sichuan Province, 646000, P.R. China
- Sichuan Treatment Center for Gynaecologic and Breast Diseases (Gynaecology), Luzhou City, Sichuan Province, 646000, P.R. China
| | - Chunyan Wang
- Department of Gynaecology, The Affiliated Hospital of Southwest Medical University, Luzhou City, Sichuan Province, 646000, P.R. China
- Sichuan Treatment Center for Gynaecologic and Breast Diseases (Gynaecology), Luzhou City, Sichuan Province, 646000, P.R. China
| | - Ping Zhan
- Department of Gynaecology, The Affiliated Hospital of Southwest Medical University, Luzhou City, Sichuan Province, 646000, P.R. China
- Sichuan Treatment Center for Gynaecologic and Breast Diseases (Gynaecology), Luzhou City, Sichuan Province, 646000, P.R. China
| | - Yaofang Liu
- Department of Reproductive Technology, The Affiliated Hospital of Southwest Medical University, No.25 Taiping Street, Luzhou City, Sichuan Province, 646000, P.R. China.
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10
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Jia Z, Wei QJ. CircRNA-MSR Regulates LPS-Induced C28/I2 Chondrocyte Injury through miR-643/MAP2K6 Signaling Pathway. Cartilage 2021; 13:785S-795S. [PMID: 34581623 PMCID: PMC8804801 DOI: 10.1177/19476035211044826] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVE Osteoarthritis (OA) is a degenerative joint disease characterized by deterioration of articular cartilage functions. Previous studies have confirmed the role of circular RNAs (circRNAs) in OA, but the role of mechanical stress-related circRNA (circRNA-MSR) in OA is unknown. DESIGN The human chondrocytes C28/I2 were cultured and treated with lipopolysaccharide (LPS) to establish the OA model. The mRNA and protein levels were measured by qRT-PCR or Western blot. Cell viability was analyzed by MTT assay. Flow cytometry was carried out to detect cell apoptosis. The levels of TNF-α, IL-1β, and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA). Pull-down assay was conducted to measure circRNA-MSR-related miRNA. Dual-luciferase reporter gene detection was performed to detect the target relationships between miR-643 and circRNA-MSR or Mitogen-activated protein kinase kinase 6 (MAP2K6). The RNA-fluorescence in situ hybridization (RNA-FISH) assay was conducted to verify the localization of circRNA-MSR and miR-643. RESULTS The expressions of circRNA-MSR were upregulated in LPS stimulated C28/I2 cells. Knockdown of circRNA-MSR can inhibit LPS-induced apoptosis, inflammatory response, and extracellular matrix (ECM) degradation, and promote cell C28/I2 cells proliferation. Moreover, circRNA-MSR directly targeted miR-643. RNA-FISH exhibited that circRNA-MSR may act as a competing endogenous RNA (ceRNA) of miR-643. Over-expression of miR-643 could alleviate LPS-induced C28/I2 chondrocyte injury and promote cell proliferation. Besides, miR-643 directly bound to MAP2K6 mRNA. MiR-643 inhibition or MAP2K6 overexpression can reverse the role of circRNA-MSR knockdown on LPS-treated chondrocytes. CONCLUSION circRNA-MSR can upregulate MAP2K6 by targeting miR-643, thereby inhibiting cell proliferation and promoting apoptosis of C28/I2 cells.
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Affiliation(s)
- Zhen Jia
- Department of Orthopedic Trauma and
Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning,
Guangxi Zhuang Autonomous Region, China
| | - Qing-Jun Wei
- Department of Orthopedic Trauma and
Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning,
Guangxi Zhuang Autonomous Region, China,Qing-Jun Wei, Department of Orthopedic
Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical
University, No. 6, Shuangyong Road, Qingxiu District, Nanning 530021, Guangxi
Zhuang Autonomous Region, China.
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11
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Bahmyari S, Jamali Z, Khatami SH, Vakili O, Roozitalab M, Savardashtaki A, Solati A, Mousavi P, Shabaninejad Z, Vakili S, Behrouj H, Ghasemi H, Movahedpour A. microRNAs in female infertility: An overview. Cell Biochem Funct 2021; 39:955-969. [PMID: 34708430 DOI: 10.1002/cbf.3671] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 10/06/2021] [Accepted: 10/08/2021] [Indexed: 12/11/2022]
Abstract
Infertility impacts a considerable number of women worldwide, and it affects different aspects of family life and society. Although female infertility is known as a multifactorial disorder, there are strong genetic and epigenetic bases. Studies revealed that miRNAs play critical roles in initiation and development of female infertility related disorders. Early diagnosis and control of these diseases is an essential key for improving disease prognosis and reducing the possibility of infertility and other side effects. Investigating the possible use of miRNAs as biomarkers and therapeutic options is valuable, and it merits attention. Thus, in this article, we reviewed research associated with female diseases and highlighted microRNAs that are related to the polycystic ovary syndrome (up to 30 miRNAs), premature ovarian failure (10 miRNAs), endometriosis (up to 15 miRNAs), uterine fibroids (up to 15 miRNAs), endometrial polyp (3 miRNAs), and pelvic inflammatory (6 miRNAs), which are involved in one or more ovarian or uterine disease-causing processes.
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Affiliation(s)
- Sedigheh Bahmyari
- Department of Reproductive Biology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zeinab Jamali
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyyed Hossein Khatami
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Omid Vakili
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mahin Roozitalab
- Department of Nursing, School of Nursing and Midwifery, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amir Savardashtaki
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Arezoo Solati
- Department of Reproductive Biology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Pegah Mousavi
- Department of Medical Genetics, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Zahra Shabaninejad
- Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.,Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sina Vakili
- Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hamid Behrouj
- Department of Clinical Biochemistry, Behbahan Faculty of Medical Sciences, Behbahan, Iran
| | - Hassan Ghasemi
- Department of Clinical Biochemistry, Abadan University of Medical Sciences, Abadan, Iran
| | - Ahmad Movahedpour
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
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12
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Liang Y, Ming Q, Shen T, Jin Y, Zhao X, Luo R, Wang J, Lu J. CircRNA circFADS2 is Downregulated in Endometritis and its Overexpression Promotes miR-643 Maturation in Human Endometrial Epithelial Cells to Suppress Cell Apoptosis. Reprod Sci 2021; 28:3508-3514. [PMID: 34478121 DOI: 10.1007/s43032-021-00720-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Accepted: 08/14/2021] [Indexed: 11/29/2022]
Abstract
CircRNA circFADS2 suppresses LPS-induced inflammation, which plays a critical role in endometritis. Our preliminary sequencing analysis revealed a positive correlation between circFADS2 and miR-643, which also play protective roles in LPS-induced inflammation. Therefore, this study was performed to explore the involvement of circFADS2 in endometritis with a focus on its interaction with miR-643. RT-qPCR was performed to analyze the levels circFADS2, mature miR-643, and premature miR-643 in plasma samples from endometritis patients (n = 66) and healthy controls (n = 66). Pearson's correlation coefficient was applied to analyze correlations between these genes. The effect of circFADS2 on miR-643 maturation was analyzed by measuring miR-643 and premature miR-643 levels in circFADS2-overexpressed human endometrial epithelial cell line HEnEpCs. The role of circFADS2 and miR-643 in HEnEpC apoptosis under LPS treatment was analyzed by cell apoptosis assay. CircFADS2 was downregulated in endometritis and was positively correlated with mature miR-643, but not premature miR-643. CircFADS2 overexpression in HEnEpCs increased the level of mature miR-643 but not premature miR-643. Cell apoptosis analysis showed that circFADS2 and miR-643 overexpression protected HEnEpCs from LPS-induced cell apoptosis, and miR-643 inhibition reduced the effect of circFADS2 overexpression. CircFADS2 is downregulated in endometritis, and it overexpression promotes miR-643 maturation in HEnEpCs to suppress cell apoptosis.
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Affiliation(s)
- Yuanjiao Liang
- Reproductive Medicine Center, Zhongda Hospital, Southeast University, No. 87 Dingjia Bridge, Gulou District, Nanjing City, Jiangsu Province, 210009, People's Republic of China
| | - Qi Ming
- Reproductive Medicine Center, Zhongda Hospital, Southeast University, No. 87 Dingjia Bridge, Gulou District, Nanjing City, Jiangsu Province, 210009, People's Republic of China
| | - Tao Shen
- Reproductive Medicine Center, Zhongda Hospital, Southeast University, No. 87 Dingjia Bridge, Gulou District, Nanjing City, Jiangsu Province, 210009, People's Republic of China
| | - Yihan Jin
- Reproductive Medicine Center, Zhongda Hospital, Southeast University, No. 87 Dingjia Bridge, Gulou District, Nanjing City, Jiangsu Province, 210009, People's Republic of China
| | - Xia Zhao
- Reproductive Medicine Center, Zhongda Hospital, Southeast University, No. 87 Dingjia Bridge, Gulou District, Nanjing City, Jiangsu Province, 210009, People's Republic of China
| | - Rong Luo
- Reproductive Medicine Center, Zhongda Hospital, Southeast University, No. 87 Dingjia Bridge, Gulou District, Nanjing City, Jiangsu Province, 210009, People's Republic of China
| | - Jiahui Wang
- Reproductive Medicine Center, Zhongda Hospital, Southeast University, No. 87 Dingjia Bridge, Gulou District, Nanjing City, Jiangsu Province, 210009, People's Republic of China
| | - Jinchun Lu
- Reproductive Medicine Center, Zhongda Hospital, Southeast University, No. 87 Dingjia Bridge, Gulou District, Nanjing City, Jiangsu Province, 210009, People's Republic of China.
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13
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Ding J, Zhang Y, Cai X, Zhang Y, Yan S, Wang J, Zhang S, Yin T, Yang C, Yang J. Extracellular vesicles derived from M1 macrophages deliver miR-146a-5p and miR-146b-5p to suppress trophoblast migration and invasion by targeting TRAF6 in recurrent spontaneous abortion. Theranostics 2021; 11:5813-5830. [PMID: 33897883 PMCID: PMC8058722 DOI: 10.7150/thno.58731] [Citation(s) in RCA: 93] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 03/07/2021] [Indexed: 12/14/2022] Open
Abstract
Rationale: Emerging evidence demonstrates that insufficient migration and invasion of trophoblasts play critical roles in the pathogenesis of recurrent spontaneous abortion (RSA). Cell-to-cell communication at the maternal-fetal interface is essential to maintain the invasion and migration of trophoblasts. M1 macrophages, important immune cellular components at the maternal-fetal interface, have been reported to be elevated in decidua tissues from patients with RSA. Recent studies indicate that M1 macrophages modulate trophoblast biological behaviors; however, the underlying mechanisms remain poorly understood. Methods: Extracellular vesicles (EVs) were isolated from the supernatant of M1 macrophages inducted from THP-1 cells (M1-EVs) by ultracentrifugation, identified by transmission electron microscopy, nanoparticle tracking analysis, and western blotting, and their miRNA profile was characterized by miRNA sequencing. Scratch wound healing and transwell assays were used to investigate the effect of M1-EVs on trophoblast migration and invasion. RT-PCR, western blotting, and luciferase reporter assays were conducted to uncover the underlying mechanism. Finally, animal experiments were employed to explore the effect of M1-EVs on embryo absorption in mice. Results: M1 macrophages suppressed trophoblast EMT to reduce their migration and invasion abilities in vitro by secreting EVs. Through miRNA sequencing, miR-146a-5p and miR-146b-5p were identified as the most upregulated miRNAs in trophoblasts treated with M1-EVs. Further functional experiments showed that M1-EVs inhibited trophoblast migration and invasion by transferring miR-146a-5p and miR-146b-5p. Mechanistically, EV miR-146a-5p and miR-146b-5p inhibited EMT of trophoblasts by directly suppressing TNF receptor-associated factor 6 (TRAF6) expression at the post-transcriptional level. Furthermore, M1-EVs aggravated embryo absorption in mice. Clinically, expression of miR-146a-5p, miR-146b-5p, and TRAF6 were aberrant in placental villous tissues from patients with RSA, and negative correlations were found between miR-146a-5p/miR-146b-5p and TRAF6 expression levels. Conclusions: Our findings indicate that miR-146a-5p and miR-146b-5p derived from EVs play important roles in intercellular communication between M1 macrophages and trophoblasts, illuminating a novel mechanism in M1 macrophage regulation of trophoblasts and their role in RSA.
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Affiliation(s)
- Jinli Ding
- Reproductive Medical Center, Renmin Hospital of Wuhan University & Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan 430060, China
| | - Yan Zhang
- Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Xiaopeng Cai
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Yi Zhang
- Reproductive Medical Center, Renmin Hospital of Wuhan University & Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan 430060, China
| | - Sisi Yan
- Reproductive Medical Center, Renmin Hospital of Wuhan University & Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan 430060, China
| | - Jiayu Wang
- Reproductive Medical Center, Renmin Hospital of Wuhan University & Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan 430060, China
| | - Sainan Zhang
- Reproductive Medical Center, Renmin Hospital of Wuhan University & Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan 430060, China
| | - Tailang Yin
- Reproductive Medical Center, Renmin Hospital of Wuhan University & Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan 430060, China
| | - Chaogang Yang
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Jing Yang
- Reproductive Medical Center, Renmin Hospital of Wuhan University & Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan 430060, China
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14
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Lv H, Yan C, Deng L, Peng Z, Yang D, Hu W, Ding X, Tong C, Wang X. Role of MicroRNAs in Protective Effects of Forsythoside A Against Lipopolysaccharide-Induced Inflammation in Bovine Endometrial Stromal Cells. Front Vet Sci 2021; 8:642913. [PMID: 33718475 PMCID: PMC7943879 DOI: 10.3389/fvets.2021.642913] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 02/02/2021] [Indexed: 12/29/2022] Open
Abstract
Bovine endometrial stromal cells (bESCs) are exposed to a complex environment of bacteria and viruses due to the rupture of epithelial cells after delivery. Inflammatory responses are elicited by the activation of host pattern recognition receptors through pathogen-related molecules such as lipopolysaccharides (LPS) on the cell membrane. Forsythoside A (FTA) is a major active constituent of Forsythia suspensa (Thunb.) Vahl. is a flowering plant widely employed as a traditional Chinese herbal medicine to treat various inflammatory diseases such as nephritis, eye swelling, scabies, ulcers, and mastitis; however, the molecular mechanisms underlying its therapeutic effects on bovine endometritis are still unclear. The aim of this study was to explore the role of miRNA and the mechanisms underlying the protective activity of FTA on the inflammation of bovine endometrial stromal cells induced by LPS. Based on previous research, we isolated and cultured bESCs in vitro and categorized them into LPS and LPS+FTA groups with three replicates. Upon reaching 80% confluence, the bESCs were treated with 0.5 μg/mL of LPS or 0.5 μg/mL of LPS + 100 μg/mL of FTA. We, then, performed high-throughput sequencing (RNA-Seq) to investigate the effects of FTA on LPS-stimulated primary bESCs and their underlying mechanisms. We identified 167 miRNAs differentially expressed in the LPS groups; 72 miRNAs were up-regulated, and 95 were down-regulated. Gene ontology enrichment analysis revealed that differentially expressed microRNA (DEGs) were most enriched during the cellular metabolic process; they were mostly located intracellularly and participated in protein, enzyme, and ion binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the DEGs were most enriched in the mitogen-activated protein kinase, tumor necrosis factor, and Interleukin-17 signaling pathways. These results reveal the complex molecular mechanism involved in the FTA and provide a basis for future studies of bovine endometritis treatment with traditional Chinese medicine monomer.
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Affiliation(s)
- Haimiao Lv
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, China
| | - Chenbo Yan
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, China
| | - Lixin Deng
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, China
| | - Zhan Peng
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, China
| | - Dexin Yang
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, China
| | - Wenjv Hu
- College of Agricultural Medicine, Henan Radio and Television University, Zhengzhou, China
| | - Xuefen Ding
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, China
| | - Chao Tong
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, China.,Wushu Overseas Students Pioneer Park, Wuhu, China
| | - Xinzhuang Wang
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, China
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15
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Pirtea P, Cicinelli E, De Nola R, de Ziegler D, Ayoubi JM. Endometrial causes of recurrent pregnancy losses: endometriosis, adenomyosis, and chronic endometritis. Fertil Steril 2021; 115:546-560. [PMID: 33581856 DOI: 10.1016/j.fertnstert.2020.12.010] [Citation(s) in RCA: 73] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 12/03/2020] [Accepted: 12/11/2020] [Indexed: 12/19/2022]
Abstract
Chronic inflammatory processes affecting the endometrium, as encountered in endometriosis, adenomyosis, and chronic endometritis, alter endometrial receptivity. These disorders are associated with early pregnancy losses and possibly recurrent pregnancy losses (RPL). In the cases of endometriosis, other factors associated with the disease also are susceptible of causing miscarriages and possibly RPL, such as an impact of intrapelvic inflammatory processes affecting the oocyte and embryo in case of natural conception. Conversely these latter effects obviously are bypassed in case of assisted reproductive technology. Chronic inflammation of the endometrium in the condition known as chronic endometritis also causes early pregnancy losses and RPL with beneficial effects achieved when specific treatment is undertaken.
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Affiliation(s)
- Paul Pirtea
- Department of Obstetrics and Gynecology and Reproductive Medicine, Hopital Foch - Faculté de Medicine Paris Ouest, Suresnes, France.
| | - Ettore Cicinelli
- Unit of Obstetrics and Gynecology, Department of Biomedical and Human Oncologic Science, University of Bari, Bari, Italy; Piazza Giulio Cesare, Policlinico, Bari, Italy
| | - Rosalba De Nola
- Unit of Obstetrics and Gynecology, Department of Biomedical and Human Oncologic Science, University of Bari, Bari, Italy; Piazza Giulio Cesare, Policlinico, Bari, Italy
| | - Dominique de Ziegler
- Department of Obstetrics and Gynecology and Reproductive Medicine, Hopital Foch - Faculté de Medicine Paris Ouest, Suresnes, France
| | - Jean Marc Ayoubi
- Department of Obstetrics and Gynecology and Reproductive Medicine, Hopital Foch - Faculté de Medicine Paris Ouest, Suresnes, France
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16
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Oladejo AO, Li Y, Wu X, Imam BH, Shen W, Ding XZ, Wang S, Yan Z. MicroRNAome: Potential and Veritable Immunomolecular Therapeutic and Diagnostic Baseline for Lingering Bovine Endometritis. Front Vet Sci 2020; 7:614054. [PMID: 33426032 PMCID: PMC7785807 DOI: 10.3389/fvets.2020.614054] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 11/18/2020] [Indexed: 12/28/2022] Open
Abstract
The bovine endometrium is a natural pathogen invasion barrier of the uterine tissues' endometrial epithelial cells that can resist foreign pathogen invasion by controlling the inflammatory immune response. Some pathogens suppress the innate immune system of the endometrium, leading to prolonged systemic inflammatory response through the blood circulation or cellular degradation resulting in bovine endometritis by bacterial endotoxins. The microRNA (miRNA) typically involves gene expression in multicellular organisms in post-transcription regulation by affecting both the stability and the translation of messenger RNA. Accumulated evidence suggests that miRNAs are important regulators of genes in several cellular processes. They are a class of endogenous non-coding RNAs, which play pivotal roles in the inflammatory response of reproductive diseases. Studies confirmed that miRNAs play a key regulatory role in various inflammatory diseases by mediating the molecular mechanism of inflammatory cytokines via signal pathways. It implicates some miRNAs in the occurrence of bovine endometritis, resorting to regulating the activities of some inflammatory cytokines, chemokine, differentially expressed genes, and protein through modulating of specific cellular signal pathways functions. This review dwells on improving the knowledge of the role of miRNAs involvement in inflammatory response as to early diagnosis, control, and prevention of bovine endometritis and consequently enlighten on the molecular improvement of the genes coded by various differentially expressed miRNA through the need to adopt recent genetic technologies and the development of new pharmaceutical preparations.
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Affiliation(s)
- Ayodele Olaolu Oladejo
- Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, Lanzhou, China.,Department of Animal Health Technology, Oyo State College of Agriculture and Technology, Igbo-Ora, Nigeria
| | - Yajuan Li
- Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, Lanzhou, China
| | - Xiaohu Wu
- Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, Lanzhou, China
| | - Bereket Habte Imam
- Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, Lanzhou, China
| | - Wenxiang Shen
- Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, Lanzhou, China
| | - Xue Zhi Ding
- Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, Lanzhou, China
| | - Shengyi Wang
- Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, Lanzhou, China
| | - Zuoting Yan
- Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, Lanzhou, China
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17
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DNaseI protects lipopolysaccharide-induced endometritis in mice by inhibiting neutrophil extracellular traps formation. Microb Pathog 2020; 150:104686. [PMID: 33309847 DOI: 10.1016/j.micpath.2020.104686] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 11/27/2020] [Accepted: 11/30/2020] [Indexed: 12/16/2022]
Abstract
Endometritis is an inflammatory of the inner lining of the uterus caused by bacterial infections that affect female reproductive health in humans and animals. Neutrophil extracellular traps (NETs) have the ability to resist infections that caused by pathogenic invasions. It has been proved that the formation of NETs is related to certain inflammatory diseases, such as mastitis and chronic obstructive pulmonary disease (COPD). However, there are sparse studies related to NETs and endometritis. In this study, we investigated the role of NETs in lipopolysaccharide (LPS)-induced acute endometritis in mice and evaluated the therapeutic efficiency of DNaseI. We established LPS-induced endometritis model in mice and found that the formation of NETs can be detected in the mice uterine tissues in vivo. In addition, DNaseI treatment can inhibit NETs construction in LPS-induced endometritis in mice. Moreover, myeloperoxidase (MPO) activity assay indicated that DNaseI treatment remarkably alleviated the inflammatory cell infiltrations. ELISA test indicated that the treatment of DNaseI significantly inhibited the expression of the proinflammatory cytokines TNF-α, and IL-1β. Also, DNaseI was found to increase proteins expression of the uterine tissue tight junctions and suppress LPS-induced NF-κB activation. All the results indicated that DNaseI effectively inhibits the formation of NETs by blocking the NF-κB signaling pathway and enhances the expression of tight junction proteins, consequently, alleviates inflammatory reactions in LPS-induced endometritis in mice.
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18
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Abstract
Tumor necrosis factor receptor (TNFR)-related factors (TRAFs) are important linker molecules in the tumor necrosis factor superfamily (TNFSF) and the Toll-like/interleukin-1 receptor (TLR/ILR) superfamily. There are seven members: TRAF1-TRAF7, among those members, tumor necrosis factor receptor-associated factor 6 (TRAF6) is upregulated in various tumors, which has been related to tumorigenesis and development. With the in-depth study of the relationship between TRAF6 and different types of tumors, TRAF6 has oncogenic characteristics involved in tumorigenesis, tumor development, invasion, and metastasis through various signaling pathways, therefore, targeting TRAF6 has provided a novel strategy for tumor treatment. This review summarizes and analyzes the role of TRAF6 in tumorigenesis and tumor development in combination with the current research on TRAF6 and tumors.
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