MicroRNA-30c suppresses the pro-fibrogenic effects of cardiac fibroblasts induced by TGF-β1 and prevents atrial fibrosis by targeting TGFβRII

J Cell Mol Med. 2018 Jun;22(6):3045-3057. doi: 10.1111/jcmm.13548. Epub 2018 Mar 13.

Abstract

Atrial fibrosis serves as an important contributor to atrial fibrillation (AF). Recent data have suggested that microRNA-30c (miR-30c) is involved in fibrotic remodelling and cancer development, but the specific role of miR-30c in atrial fibrosis remains unclear. The purpose of this study was to investigate the role of miR-30c in atrial fibrosis and its underlying mechanisms through in vivo and in vitro experiments. Our results indicate that miR-30c is significantly down-regulated in the rat abdominal aortic constriction (AAC) model and in the cellular model of fibrosis induced by transforming growth factor-β1 (TGF-β1). Overexpression of miR-30c in cardiac fibroblasts (CFs) markedly inhibits CF proliferation, differentiation, migration and collagen production, whereas decrease in miR-30c leads to the opposite results. Moreover, we identified TGFβRII as a target of miR-30c. Finally, transferring adeno-associated virus 9 (AAV9)-miR-30c into the inferior vena cava of rats attenuated fibrosis in the left atrium following AAC. These data indicate that miR-30c attenuates atrial fibrosis via inhibition of CF proliferation, differentiation, migration and collagen production by targeting TGFβRII, suggesting that miR-30c might be a novel potential therapeutic target for preventing atrial fibrosis.

Keywords: TGFβRII; atrial fibrosis; miR-30c.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrial Fibrillation / genetics*
  • Atrial Fibrillation / metabolism
  • Atrial Fibrillation / pathology
  • Cell Differentiation / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Fibrosis / genetics*
  • Fibrosis / pathology
  • HEK293 Cells
  • Heart Atria / metabolism
  • Heart Atria / pathology
  • Humans
  • MicroRNAs / genetics*
  • Myocardium / metabolism
  • Myocardium / pathology
  • Myofibroblasts / metabolism
  • Rats
  • Receptor, Transforming Growth Factor-beta Type II / genetics*
  • Transforming Growth Factor beta1 / genetics*

Substances

  • MIRN30 microRNA, rat
  • MIRN30b microRNA, human
  • MicroRNAs
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • Receptor, Transforming Growth Factor-beta Type II
  • TGFBR2 protein, human