1
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Li S, Hu W, Qian L, Sun D. Insights into non-coding RNAS: biogenesis, function and their potential regulatory roles in acute kidney disease and chronic kidney disease. Mol Cell Biochem 2025; 480:1287-1304. [PMID: 39110280 PMCID: PMC11842482 DOI: 10.1007/s11010-024-05083-0] [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: 05/05/2024] [Accepted: 07/29/2024] [Indexed: 01/03/2025]
Abstract
Noncoding RNAs (ncRNAs) have emerged as pivotal regulators of gene expression, and have attracted significant attention because of their various roles in biological processes. These molecules have transcriptional activity despite their inability to encode proteins. Moreover, research has revealed that ncRNAs, especially microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), are linked to pervasive regulators of kidney disease, including anti-inflammatory, antiapoptotic, antifibrotic, and proangiogenic actions in acute and chronic kidney disease. Although the exact therapeutic mechanism of ncRNAs remains uncertain, their value in treatment has been studied in clinical trials. The numerous renal diseases and the beneficial or harmful effects of NcRNAs on the kidney will be discussed in this article. Afterward, exploring the biological characteristics of ncRNAs, as well as their purpose and potential contributions to acute and chronic renal disease, were explored. This may offer guidance for treating both acute and long-term kidney illnesses, as well as insights into the potential use of these indicators as kidney disease biomarkers.
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Affiliation(s)
- Shulin Li
- Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Wanru Hu
- Central Laboratory, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Luoxiang Qian
- Central Laboratory, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Dong Sun
- Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
- Department of Internal Medicine and Diagnostics, Xuzhou Medical University, Xuzhou, China.
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2
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Li B, Wang J, Gao Y, Wu X, Wang C, Wang J, Liu J, Wang Y. Identifying Water-Salt Homeostasis and Inflammatory Response in Pathological Cardiac Surgery-Associated Acute Kidney Injury: NT-proBNP-related lncRNAs and miRNAs as Novel Diagnostic Biomarkers and Therapeutic Targets. Int J Med Sci 2025; 22:845-855. [PMID: 39991757 PMCID: PMC11843142 DOI: 10.7150/ijms.107589] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 01/09/2025] [Indexed: 02/25/2025] Open
Abstract
Acute kidney injury related to cardiac surgery (CS-AKI) is a serious medical issue that creates significant social and economic challenges globally. Inflammatory responses and disruptions in water and salt balance are important contributors to CS-AKI. Earlier studies indicated that pre-surgery levels of NT-proBNP were a dependable indicator of CS-AKI. Emerging evidence indicates that the abnormal expression of microRNA (miRNA) and long non-coding RNA (lncRNA) plays a role in the occurrence of CS-AKI. However, the important roles and mechanisms by which NT-proBNP affects lncRNA and miRNA in CS-AKI are still unclear. Here, we investigated lncRNA and miRNA expression patterns in BNP-high, BNP-stable, AKI, and non-AKI groups through whole transcriptome sequencing analysis. The BNP group exhibited differential expressions of 105 miRNAs and 138 lncRNAs. We identified 7 common miRNAs and lncRNAs in both the BNP and AKI groups. A functional and pathway enrichment analysis of the target genes associated with these miRNAs and lncRNAs was conducted, indicating that miR-135a-5p, miR-138-5p, miR-143-3p, and miR-206 are key factors in CS-AKI, particularly in regulating inflammatory responses and water-salt balance. These results provide fresh perspectives on research directions and possible treatment approaches for CS-AKI.
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Affiliation(s)
- Bianfang Li
- Department of Surgery Intensive Care Unit, Emergency and Critical Care Medical Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
| | - Jianhui Wang
- Department of Anesthesiology, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Yuchen Gao
- Department of Anesthesiology, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Xiaojing Wu
- Department of Surgery Intensive Care Unit, Emergency and Critical Care Medical Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
| | - Chunrong Wang
- Department of Anesthesiology, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Jin Wang
- Xianning Medical College, Hubei University of Science & Technology, Xianning 437000, China
| | - Jia Liu
- Department of Anesthesiology, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
| | - Yuefu Wang
- Department of Surgery Intensive Care Unit, Emergency and Critical Care Medical Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
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Bravo-Vázquez LA, Paul S, Colín-Jurado MG, Márquez-Gallardo LD, Castañón-Cortés LG, Banerjee A, Pathak S, Duttaroy AK. Exploring the Therapeutic Significance of microRNAs and lncRNAs in Kidney Diseases. Genes (Basel) 2024; 15:123. [PMID: 38275604 PMCID: PMC10815231 DOI: 10.3390/genes15010123] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 01/14/2024] [Accepted: 01/17/2024] [Indexed: 01/27/2024] Open
Abstract
MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two crucial classes of transcripts that belong to the major group of non-coding RNAs (ncRNAs). These RNA molecules have significant influence over diverse molecular processes due to their crucial role as regulators of gene expression. However, the dysregulated expression of these ncRNAs constitutes a fundamental factor in the etiology and progression of a wide variety of multifaceted human diseases, including kidney diseases. In this context, over the past years, compelling evidence has shown that miRNAs and lncRNAs could be prospective targets for the development of next-generation drugs against kidney diseases as they participate in a number of disease-associated processes, such as podocyte and nephron death, renal fibrosis, inflammation, transition from acute kidney injury to chronic kidney disease, renal vascular changes, sepsis, pyroptosis, and apoptosis. Hence, in this current review, we critically analyze the recent findings concerning the therapeutic inferences of miRNAs and lncRNAs in the pathophysiological context of kidney diseases. Additionally, with the aim of driving advances in the formulation of ncRNA-based drugs tailored for the management of kidney diseases, we discuss some of the key challenges and future prospects that should be addressed in forthcoming investigations.
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Affiliation(s)
- Luis Alberto Bravo-Vázquez
- School of Engineering and Sciences, Tecnologico de Monterrey, Campus Queretaro, Av. Epigmenio Gonzalez, No. 500 Fracc. San Pablo, Queretaro 76130, Mexico (S.P.)
| | - Sujay Paul
- School of Engineering and Sciences, Tecnologico de Monterrey, Campus Queretaro, Av. Epigmenio Gonzalez, No. 500 Fracc. San Pablo, Queretaro 76130, Mexico (S.P.)
| | - Miriam Guadalupe Colín-Jurado
- School of Engineering and Sciences, Tecnologico de Monterrey, Campus Queretaro, Av. Epigmenio Gonzalez, No. 500 Fracc. San Pablo, Queretaro 76130, Mexico (S.P.)
| | - Luis David Márquez-Gallardo
- School of Engineering and Sciences, Tecnologico de Monterrey, Campus Queretaro, Av. Epigmenio Gonzalez, No. 500 Fracc. San Pablo, Queretaro 76130, Mexico (S.P.)
| | - Luis Germán Castañón-Cortés
- School of Engineering and Sciences, Tecnologico de Monterrey, Campus Queretaro, Av. Epigmenio Gonzalez, No. 500 Fracc. San Pablo, Queretaro 76130, Mexico (S.P.)
| | - Antara Banerjee
- Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chennai 603103, India
| | - Surajit Pathak
- Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chennai 603103, India
| | - Asim K. Duttaroy
- Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, N-0316 Oslo, Norway
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Wang Z, Liu L, Li Z, Liu X, Wang J, Wang J, Jiang G, Yu H. LncRNA LINC01278 Regulates the Prognosis and Related Mechanisms of Gastric Cancer by Targeting miR-129-5p. J Environ Pathol Toxicol Oncol 2024; 43:43-52. [PMID: 39016140 DOI: 10.1615/jenvironpatholtoxicoloncol.2024053208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/18/2024] Open
Abstract
Gastric cancer, a prevalent malady within the digestive tract, has a complex pathological mechanism and numerous patients. The regulation of gastric cancer process by long non-coding RNA (lncRNA) presented new prospects for the study of its molecular mechanism and the treatment of patients. The abnormal expressed genes in gastric cancer were screened by GSE193109 dataset. The correlation between LINC01278 and the likelihood of survival in patients suffering from gastric cancer was investigated by Kaplan-Meier survival curve and multivariate Cox analysis. LINC01278 in gastric cancer tissue samples and cells was verified via RT-qPCR. The cell counting kit-8 (CCK-8) and transwell assay were selected to detect the growth activity of gastric cancer cells. The association between LINC01278 and miR-129-5p was validated through luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) assay. Correlation analysis of clinical features revealed an association between LINC01278 and the prognosis in gastric cancer patients. LINC01278 was actively expressed in gastric cancer, which exerts a tumor-promoting effect. Silencing LINC01278 suppressed the biological function of tumor cells through spongiform miR-129-5p. LINC01278 has the potential to serve as a novel biomarker, offering new avenues of research for the prognosis and treatment of gastric cancer.
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Affiliation(s)
- Zhenhua Wang
- Department of Hepatobiliary Pancreatogastric Surgery, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Caner Hospital Chinese Academy of Medical Science/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, 030013, China
| | - Liyan Liu
- Department of Gastroenterology, Jilin Province FAW General Hospital, Changchun, 130013, China
| | - Zhengliang Li
- Second Department of Radiotherapy, Yantaishan Hospital, Yantai, 264003, China
| | - Xiaojing Liu
- Department of Traditional Chinese Medicine, Yantai Center for Food and Drug Control, Yantai, 264003, China
| | - Jundong Wang
- Department of Traditional Chinese Medicine, Yantai Center for Food and Drug Control, Yantai, 264003, China
| | - Jiaxi Wang
- Department of Business Management Division II, Yantai Center for Food and Drug Control, Yantai, 264003, China
| | - Guoxiang Jiang
- Second Department of Radiotherapy, Yantaishan Hospital, Yantai, 264003, China
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Jin C, Cao Y, Li Y. Bone Mesenchymal Stem Cells Origin Exosomes are Effective Against Sepsis-Induced Acute Kidney Injury in Rat Model. Int J Nanomedicine 2023; 18:7745-7758. [PMID: 38144514 PMCID: PMC10743757 DOI: 10.2147/ijn.s417627] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Accepted: 12/13/2023] [Indexed: 12/26/2023] Open
Abstract
Introduction The incidence and mortality rates of sepsis-induced acute kidney injury (SAKI) remain high, posing a substantial healthcare burden. Studies have implicated a connection between the development of SAKI and inflammation response, apoptosis, and autophagy. Moreover, evidence suggests that manipulating autophagy could potentially influence the prognosis of this condition. Notably, exosomes derived from bone mesenchymal stem cells (BMSCs-Exo) have exhibited promise in mitigating cellular damage by modulating pathways associated with inflammation, apoptosis, and autophagy. Thus, this study aims to investigate the influence of BMSCs-Exo on SAKI and the potential mechanisms that drive this impact. Methods The SAKI model was induced in HK-2 cells using lipopolysaccharide (LPS), while rats underwent cecal ligation and puncture (CLP) to simulate the condition. Cell viability was assessed using the CCK-8 kit, and kidney damage was evaluated through HE staining, blood urea nitrogen (BUN), and serum creatinine (SCr) measurements. Inflammatory-related RNAs and proteins were quantified via qPCR and ELISA, respectively. Apoptosis was determined through apoptosis-related protein levels, flow cytometry, and TUNEL staining. Western blot analysis was utilized to measure associated protein expressions. Results In vivo, BMSCs-Exo ameliorated kidney injury in CLP-induced SAKI rats, reducing inflammatory cytokine production and apoptosis levels. Fluorescence microscope observed the absorption of BMSCs-Exo by renal cells following injection via tail vein. In the SAKI rat kidney tissue, there was an upregulation of LC3-II/LC3-I, p62, and phosphorylated AMP-activated protein kinase (p-AMPK) expressions, indicating blocked autophagic flux, while phosphorylated mammalian target of rapamycin (p-mTOR) expression was downregulated. However, BMSCs-Exo enhanced LC3-II/LC3-I and p-AMPK expression, concurrently reducing p62 and p-mTOR levels. In vitro, BMSCs-Exo enhanced cell viability in LPS-treated HK-2 cells, and exerted anti-inflammation and anti-apoptosis effects which were consistent with the results in vivo. Similarly, rapamycin (Rapa) exhibited a protective effect comparable to BMSCs-Exo, albeit partially abrogated by 3-methyladenine (3-MA). Conclusion BMSCs-Exo mitigate inflammation and apoptosis through autophagy in SAKI, offering a promising avenue for SAKI treatment.
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Affiliation(s)
- Cui Jin
- Department of Critical Care Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China
| | - Yongmei Cao
- Department of Critical Care Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China
| | - Yingchuan Li
- Department of Critical Care Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China
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Rahbar Saadat Y, Hosseiniyan Khatibi SM, Sani A, Zununi Vahed S, Ardalan M. Ischemic tubular injury: Oxygen-sensitive signals and metabolic reprogramming. Inflammopharmacology 2023; 31:1657-1669. [PMID: 37131045 DOI: 10.1007/s10787-023-01232-x] [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: 07/23/2022] [Accepted: 03/21/2023] [Indexed: 05/04/2023]
Abstract
The kidneys are the most vulnerable organs to severe ischemic insult that results in cellular hypoxia under pathophysiological conditions. Large amounts of oxygen are consumed by the kidneys, mainly to produce energy for tubular reabsorption. Beyond high oxygen demand and the low oxygen supply, different other factors make kidneys vulnerable to ischemia which is deemed to be a major cause of acute kidney injury (AKI). On the other hand, kidneys are capable of sensing and responding to oxygen alternations to evade harms resulting from inadequate oxygen. The hypoxia-inducible factor (HIF) is the main conserved oxygen-sensing mechanism that maintains homeostasis under hypoxia through direct/indirect regulation of several genes that contribute to metabolic adaptation, angiogenesis, energy conservation, erythropoiesis, and so on. In response to oxygen availability, prolyl-hydroxylases (PHDs) control the HIF stability. This review focuses on the oxygen-sensing mechanisms in kidneys, particularly in proximal tubular cells (PTCs) and discusses the molecules involved in ischemic response and metabolic reprogramming. Moreover, the possible roles of non-coding RNAs (microRNAs and long non-coding RNAs) in the development of ischemic AKI are put forward.
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Affiliation(s)
| | | | - Anis Sani
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
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7
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Giannuzzi F, Maiullari S, Gesualdo L, Sallustio F. The Mission of Long Non-Coding RNAs in Human Adult Renal Stem/Progenitor Cells and Renal Diseases. Cells 2023; 12:1115. [PMID: 37190024 PMCID: PMC10137190 DOI: 10.3390/cells12081115] [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: 02/20/2023] [Revised: 03/29/2023] [Accepted: 04/06/2023] [Indexed: 05/17/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) are a large, heterogeneous class of transcripts and key regulators of gene expression at both the transcriptional and post-transcriptional levels in different cellular contexts and biological processes. Understanding the potential mechanisms of action of lncRNAs and their role in disease onset and development may open up new possibilities for therapeutic approaches in the future. LncRNAs also play an important role in renal pathogenesis. However, little is known about lncRNAs that are expressed in the healthy kidney and that are involved in renal cell homeostasis and development, and even less is known about lncRNAs involved in human adult renal stem/progenitor cells (ARPC) homeostasis. Here we give a thorough overview of the biogenesis, degradation, and functions of lncRNAs and highlight our current understanding of their functional roles in kidney diseases. We also discuss how lncRNAs regulate stem cell biology, focusing finally on their role in human adult renal stem/progenitor cells, in which the lncRNA HOTAIR prevents them from becoming senescent and supports these cells to secrete high quantities of α-Klotho, an anti-aging protein capable of influencing the surrounding tissues and therefore modulating the renal aging.
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Affiliation(s)
- Francesca Giannuzzi
- Department of Interdisciplinary Medicine (DIM), University of Bari Aldo Moro, 70124 Bari, Italy
| | - Silvia Maiullari
- Department of Interdisciplinary Medicine (DIM), University of Bari Aldo Moro, 70124 Bari, Italy
| | - Loreto Gesualdo
- Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, 70124 Bari, Italy
- MIRROR—Medical Institute for Regeneration, Repairing and Organ Replacement, Interdepartmental Center, University of Bari Aldo Moro, 70124 Bari, Italy
| | - Fabio Sallustio
- Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, 70124 Bari, Italy
- MIRROR—Medical Institute for Regeneration, Repairing and Organ Replacement, Interdepartmental Center, University of Bari Aldo Moro, 70124 Bari, Italy
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8
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Huang R, Fu P, Ma L. Kidney fibrosis: from mechanisms to therapeutic medicines. Signal Transduct Target Ther 2023; 8:129. [PMID: 36932062 PMCID: PMC10023808 DOI: 10.1038/s41392-023-01379-7] [Citation(s) in RCA: 241] [Impact Index Per Article: 120.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 02/12/2023] [Accepted: 02/20/2023] [Indexed: 03/19/2023] Open
Abstract
Chronic kidney disease (CKD) is estimated to affect 10-14% of global population. Kidney fibrosis, characterized by excessive extracellular matrix deposition leading to scarring, is a hallmark manifestation in different progressive CKD; However, at present no antifibrotic therapies against CKD exist. Kidney fibrosis is identified by tubule atrophy, interstitial chronic inflammation and fibrogenesis, glomerulosclerosis, and vascular rarefaction. Fibrotic niche, where organ fibrosis initiates, is a complex interplay between injured parenchyma (like tubular cells) and multiple non-parenchymal cell lineages (immune and mesenchymal cells) located spatially within scarring areas. Although the mechanisms of kidney fibrosis are complicated due to the kinds of cells involved, with the help of single-cell technology, many key questions have been explored, such as what kind of renal tubules are profibrotic, where myofibroblasts originate, which immune cells are involved, and how cells communicate with each other. In addition, genetics and epigenetics are deeper mechanisms that regulate kidney fibrosis. And the reversible nature of epigenetic changes including DNA methylation, RNA interference, and chromatin remodeling, gives an opportunity to stop or reverse kidney fibrosis by therapeutic strategies. More marketed (e.g., RAS blockage, SGLT2 inhibitors) have been developed to delay CKD progression in recent years. Furthermore, a better understanding of renal fibrosis is also favored to discover biomarkers of fibrotic injury. In the review, we update recent advances in the mechanism of renal fibrosis and summarize novel biomarkers and antifibrotic treatment for CKD.
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Affiliation(s)
- Rongshuang Huang
- Kidney Research Institute, Division of Nephrology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Ping Fu
- Kidney Research Institute, Division of Nephrology, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Liang Ma
- Kidney Research Institute, Division of Nephrology, West China Hospital, Sichuan University, Chengdu, 610041, China.
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9
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Li C, Meng X, Wang L, Dai X. Mechanism of action of non-coding RNAs and traditional Chinese medicine in myocardial fibrosis: Focus on the TGF-β/Smad signaling pathway. Front Pharmacol 2023; 14:1092148. [PMID: 36843918 PMCID: PMC9947662 DOI: 10.3389/fphar.2023.1092148] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 01/30/2023] [Indexed: 02/11/2023] Open
Abstract
Cardiac fibrosis is a serious public health problem worldwide that is closely linked to progression of many cardiovascular diseases (CVDs) and adversely affects both the disease process and clinical prognosis. Numerous studies have shown that the TGF-β/Smad signaling pathway plays a key role in the progression of cardiac fibrosis. Therefore, targeted inhibition of the TGF-β/Smad signaling pathway may be a therapeutic measure for cardiac fibrosis. Currently, as the investigation on non-coding RNAs (ncRNAs) move forward, a variety of ncRNAs targeting TGF-β and its downstream Smad proteins have attracted high attention. Besides, Traditional Chinese Medicine (TCM) has been widely used in treating the cardiac fibrosis. As more and more molecular mechanisms of natural products, herbal formulas, and proprietary Chinese medicines are revealed, TCM has been proven to act on cardiac fibrosis by modulating multiple targets and signaling pathways, especially the TGF-β/Smad. Therefore, this work summarizes the roles of TGF-β/Smad classical and non-classical signaling pathways in the cardiac fibrosis, and discusses the recent research advances in ncRNAs targeting the TGF-β/Smad signaling pathway and TCM against cardiac fibrosis. It is hoped, in this way, to give new insights into the prevention and treatment of cardiac fibrosis.
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Affiliation(s)
- Chunjun Li
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xiangxiang Meng
- College of Marxism, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Lina Wang
- First College of Clinical Medical, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xia Dai
- College of Health, Shandong University of Traditional Chinese Medicine, Jinan, China,*Correspondence: Xia Dai,
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Liu C, Ma K, Zhang Y, He X, Song L, Chi M, Han Z, Li G, Zhang Q, Liu C. Kidney diseases and long non-coding RNAs in the limelight. Front Physiol 2022; 13:932693. [PMID: 36299256 PMCID: PMC9589442 DOI: 10.3389/fphys.2022.932693] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Accepted: 09/21/2022] [Indexed: 11/13/2022] Open
Abstract
The most extensively and well-investigated sequences in the human genome are protein-coding genes, while large numbers of non-coding sequences exist in the human body and are even more diverse with more potential roles than coding sequences. With the unveiling of non-coding RNA research, long-stranded non-coding RNAs (lncRNAs), a class of transcripts >200 nucleotides in length primarily expressed in the nucleus and rarely in the cytoplasm, have drawn our attention. LncRNAs are involved in various levels of gene regulatory processes, including but not limited to promoter activity, epigenetics, translation and transcription efficiency, and intracellular transport. They are also dysregulated in various pathophysiological processes, especially in diseases and cancers involving genomic imprinting. In recent years, numerous studies have linked lncRNAs to the pathophysiology of various kidney diseases. This review summarizes the molecular mechanisms involved in lncRNAs, their impact on kidney diseases, and associated complications, as well as the value of lncRNAs as emerging biomarkers for the prevention and prognosis of kidney diseases, suggesting their potential as new therapeutic tools.
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Affiliation(s)
- Chenxin Liu
- Reproductive and Women-Children Hospital, School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Kuai Ma
- Department of Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yunchao Zhang
- Reproductive and Women-Children Hospital, School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xing He
- School of Clinical Medicine, Chengdu Medical College, Chengdu, China
| | - Linjiang Song
- Reproductive and Women-Children Hospital, School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Mingxuan Chi
- Department of Nephrology, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, Sichuan Renal Disease Clinical Research Center, University of Electronic Science and Technology of China, Chengdu, China
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
| | - Zhongyu Han
- Reproductive and Women-Children Hospital, School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Guanhua Li
- Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- *Correspondence: Guanhua Li, ; Qinxiu Zhang, ; Chi Liu,
| | - Qinxiu Zhang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- *Correspondence: Guanhua Li, ; Qinxiu Zhang, ; Chi Liu,
| | - Chi Liu
- Department of Nephrology, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, Sichuan Renal Disease Clinical Research Center, University of Electronic Science and Technology of China, Chengdu, China
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
- *Correspondence: Guanhua Li, ; Qinxiu Zhang, ; Chi Liu,
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Xie KH, Liu XH, Jia J, Zhong X, Han RY, Tan RZ, Wang L. Hederagenin ameliorates cisplatin-induced acute kidney injury via inhibiting long non-coding RNA A330074k22Rik/Axin2/β-catenin signalling pathway. Int Immunopharmacol 2022; 112:109247. [PMID: 36155281 DOI: 10.1016/j.intimp.2022.109247] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Revised: 08/30/2022] [Accepted: 09/09/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND Acute kidney injury (AKI), a kidney disease with high morbidity and mortality, is characterized by a dramatic decline in renal function. Hederagenin (HDG), a pentacyclic triterpenoid saponin isolated from astragalus membranaceus, has been shown to have significant anti-inflammatory effects on various diseases. However, the effects of HDG on renal injury and inflammation in AKI has not been elucidated. METHODS In this research, mice model of AKI was established by intraperitoneal injection of cisplatin in vivo, the inflammatory model of renal tubular epithelial cells was established by LPS stimulation in vitro, and HDG was used to intervene in vitro and in vivo models. Transcriptome sequencing was used to analyze the alterations of LncRNA and mRNA expression in AKI model and LncRNA-A330074k22Rik (A33) knockdown cells, respectively. Renal in situ electrotransfer knockdown plasmid was used to establish mice model of AKI with low expression of A33 in kidney. RESULTS The results showed that HDG effectively alleviate cisplatin-induced kidney injury and inflammation in mice. Transcriptome sequencing results showed that multiple LncRNAs in kidney of AKI model exhibited significant changes, among which LncRNA-A33 had the most obvious change trend. Subsequent results showed that A33 was highly expressed in kidney of AKI mice and LPS-induced renal tubular cells. After in situ renal electroporation knockdown plasmid down-regulated A33 in kidney of AKI mice, it was found that inhibition of A33 could significantly relieve cisplatin-induced kidney injury and inflammation of AKI, while HDG could effectively suppress the expression of A33 in vitro and in vivo, respectively. Subsequently, transcriptome sequencing was again used to analyze the changes in mRNA expression of renal tubular cells after A33 knockdown by siRNA. The results showed that a large number of inflammation-related signaling pathways were down-regulated, Axin2 and its downstream β-catenin signal were significantly inhibited. Cell recovery test showed that HDG inhibited Axin2/β-catenin signal by down-regulating A33, and improved kidney injury and inflammation of AKI. CONCLUSION Taken together, HDG significantly ameliorated cisplatin-induced kidney injury through LncRNA-A330074k22Rik/Axin2/β-catenin signal axis, which providing a potential therapeutic approach for the treatment of AKI.
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Affiliation(s)
- Ke-Huan Xie
- Research Center of Intergated Traditional Chinese and Western Medicine, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China
| | - Xiao-Heng Liu
- Research Center of Intergated Traditional Chinese and Western Medicine, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China
| | - Jian Jia
- Research Center of Intergated Traditional Chinese and Western Medicine, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China
| | - Xia Zhong
- Research Center of Intergated Traditional Chinese and Western Medicine, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China
| | - Rang-Yue Han
- Research Center of Intergated Traditional Chinese and Western Medicine, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China
| | - Rui-Zhi Tan
- Research Center of Intergated Traditional Chinese and Western Medicine, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China; Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, China.
| | - Li Wang
- Research Center of Intergated Traditional Chinese and Western Medicine, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China; Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, China.
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12
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Wang M, Jiang F, Zhang L, Zhang J, Xie H. Knockdown of P2Y4 ameliorates sepsis-induced acute kidney injury in mice via inhibiting the activation of the NF-κB/MMP8 axis. Front Physiol 2022; 13:953977. [PMID: 36105291 PMCID: PMC9467379 DOI: 10.3389/fphys.2022.953977] [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: 05/26/2022] [Accepted: 07/21/2022] [Indexed: 11/16/2022] Open
Abstract
Sepsis-induced acute kidney injury (S-AKI) has emerged as a frequent and life-threatening complication in critically ill patients, which is characterized by a systematic inflammatory response and a rapid decline in kidney function. P2Y4, a member of G protein–coupled P2Y nucleotide receptor family, has been reported to serve as a crucial player in inflammatory responses during the development of neurocognitive disorder and myocardial infarction. Nonetheless, the biological role of P2Y4 in S-AKI remains largely unclear. This study aimed to decipher the biological role of P2Y4 in S-AKI and illuminate the potential mechanisms. In this study, S-AKI models were successfully established in mice via cecal ligation and puncture. Results showed that the kidney tissues from S-AKI mouse models exhibited a higher P2Y4 expression level than from the sham-operated group. Knockdown of P2Y4 was found to remarkably alleviate kidney damage and reduce inflammatory response in mice of S-AKI models. Moreover, P2Y4 ablation inhibited the activation of the NF-κB/MMP-8 signaling axis. Additionally, mechanistic studies revealed that rescuing MMP-8 reversed the alleviating effects of P2Y4 knockdown against renal cell damage. Collectively, our findings indicate that P2Y4 knockdown ameliorated S-AKI in mice via inhibiting the activation of the NF-κB/MMP-8 axis and that P2Y4 may represent a novel therapeutic target for S-AKI patients.
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