MicroRNA-92a inhibition attenuates hypoxia/reoxygenation-induced myocardiocyte apoptosis by targeting Smad7

Busheng Zhang; Mi Zhou; Canbo Li; Jingxin Zhou; Haiqing Li; Dan Zhu; Zhe Wang; Anqing Chen; Qiang Zhao

doi:10.1371/journal.pone.0100298

MicroRNA-92a inhibition attenuates hypoxia/reoxygenation-induced myocardiocyte apoptosis by targeting Smad7

PLoS One. 2014 Jun 18;9(6):e100298. doi: 10.1371/journal.pone.0100298. eCollection 2014.

Authors

Busheng Zhang¹, Mi Zhou¹, Canbo Li¹, Jingxin Zhou¹, Haiqing Li¹, Dan Zhu¹, Zhe Wang¹, Anqing Chen¹, Qiang Zhao¹

Affiliation

¹ Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Abstract

Background: MicroRNAs (miRNAs) regulate a lot of physiological and pathological processes, including myocardial ischemia/reperfusion. Recent studies reported that knockdown of miR-92a could attenuate ischemia/reperfusion-induced myocardial injury. In the present study, we examined the potential anti-apoptotic effects of miR-92a in a rat myocardiocyte cell line, and the possible role of Smad7 in such actions.

Methodology and results: In a preliminary bioinformatic analysis, we identified SMAD family member 7 (Smad7) as a potential target for miR-92a. A luciferase reporter assay indeed demonstrated that miR-92a could inhibit Smad7 expression. Myocardial ischemia/reperfusion was simulated in rat H9c2 cells with 24-h hypoxia followed by 12-h reoxygenation. Prior to hypoxia/reoxygenation, cells were transfected by miR-92a inhibitor. In some experiments, cells were co-transfected with siRNA-Smad7. The miR-92a inhibitor dramatically reduced the release of lactate dehydrogenase and malonaldehyde, and attenuated cardiomyocyte apoptosis. The miR-92a inhibitor increased SMAD7 protein level and decreased nuclear NF-κB p65 protein. Effects of the miR-92a inhibitor were attenuated by co-transfection with siRNA-Smad7.

Conclusion: Inhibiting miR-92a can attenuate myocardiocyte apoptosis induced by hypoxia/reoxygenation by targeting Smad7.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects
Cell Hypoxia
Cell Line
Gene Expression Regulation
L-Lactate Dehydrogenase / metabolism
Malondialdehyde / metabolism
MicroRNAs / antagonists & inhibitors
MicroRNAs / genetics*
MicroRNAs / metabolism
Models, Biological
Molecular Mimicry
Myocardial Reperfusion Injury / genetics
Myocardial Reperfusion Injury / metabolism
Myocardial Reperfusion Injury / pathology
Myocytes, Cardiac / drug effects
Myocytes, Cardiac / metabolism*
Myocytes, Cardiac / pathology
Oligonucleotides / pharmacology
Oxygen / pharmacology
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Rats
Signal Transduction
Smad7 Protein / antagonists & inhibitors
Smad7 Protein / genetics*
Smad7 Protein / metabolism
Transcription Factor RelA / antagonists & inhibitors
Transcription Factor RelA / genetics*
Transcription Factor RelA / metabolism

Substances

MIRN92 microRNA, rat
MicroRNAs
Oligonucleotides
RNA, Small Interfering
Rela protein, rat
Smad7 Protein
Smad7 protein, rat
Transcription Factor RelA
Malondialdehyde
L-Lactate Dehydrogenase
Oxygen

Grants and funding

This work is supported by Science and Technology Commission of Shanghai Municipality of China (11JC1408000) and the National Natural Science Foundation of China (Grant No. 81200093). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.