microRNA-135a protects against myocardial ischemia-reperfusion injury in rats by targeting protein tyrosine phosphatase 1B

J Cell Biochem. 2019 Jun;120(6):10421-10433. doi: 10.1002/jcb.28327. Epub 2019 Jan 15.

Abstract

microRNAs are an emerging class of molecules that regulate pathogenesis of cardiovascular diseases. Here we aim to elucidate the effects and mechanism of miR-135a, a previously reported regulator of ischemia-reperfusion (I/R) injury, in myocardial I/R injury. Quantitative real-time polymerase chain reaction analysis revealed that the expression level of miR-135a was significantly decreased both in the rat I/R group and H9c2 cells subjected to hypoxia/reoxygenation. Overexpression of miR-135a in vivo markedly decreased the infarct size and inhibited the I/R-induced cardiomyocyte apoptosis. Overexpression of miR-135a in H9c2 also exerted antiapoptosis effects. Furthermore, bioinformatics analysis, luciferase activity, and the Western blot assay indicated that protein tyrosine phosphatase 1B (PTP1B) is a direct target of miR-135a. In addition, the expression of proapoptotic-related genes, such as p53, Bax, and cleaved caspase3, were decreased in association with the downregulation of PTP1B. In summary, this study demonstrates that miR-135a exerts protective effects against myocardial I/R injury by targeting PTP1B.

Keywords: cardiovascular; microRNA-135a; myocardial ischemia-reperfusion injury; protein tyrosine phosphatase 1B.

MeSH terms

  • Animals
  • Apoptosis
  • Gene Expression Regulation*
  • Male
  • MicroRNAs / genetics*
  • Myocardial Reperfusion Injury / etiology
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Protective Agents*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • MIRN135 microRNA, rat
  • MicroRNAs
  • Protective Agents
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Ptpn1 protein, rat