MicroRNA-142-3p inhibits hypoxia/reoxygenation‑induced apoptosis and fibrosis of cardiomyocytes by targeting high mobility group box 1

Wang,Yi; Ouyang,Min; Wang,Qiong; Jian,Zaijin

doi:10.3892/ijmm.2016.2756

MicroRNA-142-3p inhibits hypoxia/reoxygenation‑induced apoptosis and fibrosis of cardiomyocytes by targeting high mobility group box 1

Authors:
- Yi Wang
- Min Ouyang
- Qiong Wang
- Zaijin Jian
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Affiliations: Geriatric Department, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China
Published online on: September 28, 2016 https://doi.org/10.3892/ijmm.2016.2756
Pages: 1377-1386
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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