Targeting the MicroRNA-490-3p-ATG4B-Autophagy Axis Relieves Myocardial Injury in Ischemia Reperfusion

J Cardiovasc Transl Res. 2021 Feb;14(1):173-183. doi: 10.1007/s12265-020-09972-9. Epub 2020 May 31.

Abstract

We investigated the potential role of miR-490-3p in ischemia reperfusion (IR) injury. We first determined the expression of miR-490-3p and autophagy-related 4B cysteine (ATG4B) in IR. Then, to explore whether miR-490-3p would affect autophagy, apoptosis, and IR injury, we evaluated apoptosis, autophagy, and infarct size via gain- and loss-of-function experiments. Furthermore, we used adenovirus to enhance or inhibit the expression of ATG4B, and then measured autophagy, apoptosis, and IR injury. miR-490-3p was downregulated in the hearts during the process of IR, while ATG4B was upregulated. The inhibition of miR-490-3p or overexpression of ATG4B could promote the expression of LC3II, increase the autolysosomes, inhibit the expression of p62, and reduce infarct size. On all accounts, the inhibition of miR-490-3p could promote autophagy to reduce myocardial IR injury by upregulating ATG4B, a finding that provides new insights for the protective mechanism of autophagy in IR. Graphical Abstract.

Keywords: Apoptosis; Autophagy; Autophagy-related 4B cysteine; Ischemia reperfusion; microRNA-490-3p.

MeSH terms

  • Animals
  • Apoptosis
  • Autophagy
  • Autophagy-Related Proteins / biosynthesis
  • Autophagy-Related Proteins / genetics*
  • Cysteine Endopeptidases / biosynthesis
  • Cysteine Endopeptidases / genetics*
  • Disease Models, Animal
  • Gene Expression Regulation*
  • Mice
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Myocardial Reperfusion Injury / genetics*
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • RNA / genetics

Substances

  • Autophagy-Related Proteins
  • MIRN490 microRNA, mouse
  • MicroRNAs
  • RNA
  • Atg4b protein, mouse
  • Cysteine Endopeptidases