MicroRNA-142-3p inhibits hypoxia/reoxygenation-induced apoptosis and fibrosis of cardiomyocytes by targeting high mobility group box 1
Autor: | Qiong Wang, Min Ouyang, Yi Wang, Zaijin Jian |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
high mobility group box 1 Cardiac fibrosis microRNA-142-3p Blotting Western cardiomyocyte Apoptosis Real-Time Polymerase Chain Reaction HMGB1 Cell Line Transforming Growth Factor beta1 Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Fibrosis Genetics medicine Animals Myocytes Cardiac RNA Messenger Smad3 Protein HMGB1 Protein Phosphorylation Base Sequence biology Oncogene Cell growth fibrosis Transdifferentiation Articles General Medicine Flow Cytometry medicine.disease Cell Hypoxia Cell biology Oxygen MicroRNAs 030104 developmental biology Gene Knockdown Techniques 030220 oncology & carcinogenesis biology.protein hypoxia/reoxygenation Signal Transduction |
Zdroj: | International Journal of Molecular Medicine |
ISSN: | 1791-244X 1107-3756 |
Popis: | Myocardial ischemia/reperfusion (I/R) injury may cause the apoptosis of cardiomyocytes as well as cardiac fibrosis, which is characterized as the transdifferentiation of fibroblasts to myofibroblasts and collagen deposition. MicroRNAs (miRNAs or miRs) have been demonstrated to be involved in myocardial I/R injury. However, the underlying molecular mechanism remains largely unclear. In the present study, mouse cardiomyocyte M6200 cells were treated with hypoxia/reoxygenation (H/R). Our data indicated that H/R treatment led to cell apoptosis, the increased expression of fibrosis‑related proteins, namely collagen I, II, III, and fibronectin, as well as the downregulation of miR-142-3p in M6200 cells. Overexpression of miR-142-3p suppressed the H/R-induced apoptosis and fibrosis of M6200 cells. Bioinformatics analysis and a Dual‑Luciferase reporter assay further identified high mobility group box 1 (HMGB1) as a direct target gene of miR-142-3p, and miR-142-3p negatively regulated the protein level of HMGB1 in M6200 cells. Furthermore, knockdown of HMGB1 enhanced cell proliferation whereas it inhibited the apoptosis and fibrosis of M6200 cells. In addition, TGF-β1/Smad3 signaling was suggested to be involved in the miR-142-3p/HMGB1-mediated apoptosis and fibrosis of M6200 cells treated with H/R. Taken together, the findings of the present study demonstrate that miR-142-3p inhibits H/R-induced apoptosis and fibrosis of cardiomyocytes, partly at least, by the direct inhibition of HMGB1 expression. Therefore, these findings have increased our understanding of the pathogenesis of H/R-induced myocardial injury. |
Databáze: | OpenAIRE |
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