miR-483-3p regulates hyperglycaemia-induced cardiomyocyte apoptosis in transgenic mice

Biochem Biophys Res Commun. 2016 Sep 2;477(4):541-547. doi: 10.1016/j.bbrc.2016.06.051. Epub 2016 Jun 23.

Abstract

Diabetic cardiomyopathy represents severe heart complications, and is the leading cause of morbidity and mortality among patients with diabetes. Although a few microRNAs (miRNAs) have been implicated in diabetes-related complications, a functional association between miRNAs and cardiac dysfunction in diabetic cardiomyopathy remains to be demonstrated. Our results show that miR-483-3p is upregulated in streptozotocin-induced diabetic mice, and cultured cardiomyocytes mimicking hyperglycemia. Overexpressing miR-483-3p in transgenic mice with diabetes mellitus (DM) exacerbated cardiomyocyte apoptosis by transcriptionally repressing insulin growth factor 1 (IGF1). Therefore, we have uncovered a novel signaling pathway, involving miR-483-3p-IGF1, that promotes myocardial cell apoptosis under high blood-glucose condition. Further, our study indicates that miR-483-3p could be a potential therapeutic target for managing diabetes-associated heart complications.

Keywords: Apoptosis; Diabetic cardiomyopathy; IGF1; MicroRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Cell Line
  • Diabetes Mellitus, Experimental / genetics
  • Hyperglycemia / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs / genetics*
  • Myocytes, Cardiac / pathology*
  • Rats
  • Streptozocin

Substances

  • MicroRNAs
  • Mirn483 microRNA, mouse
  • Streptozocin