MiR-324-3p Regulates Fibroblast Proliferation via Targeting TGF-β1 in Atrial Fibrillation

Int Heart J. 2020 Nov 28;61(6):1270-1278. doi: 10.1536/ihj.20-423. Epub 2020 Nov 13.

Abstract

Atrial fibrillation (AF), one of the common clinical arrhythmias, lacks effective treatment manners. Cardiac fibroblasts play an essential role in myocardial fibrosis and cardiac remodeling, which are involved in AF progression. Reportedly, MicroRNAs (miRNAs) regulate the myocardial fibrosis in AF. However, whether miR-324-3p involves myocardial fibrosis in AF and the tentative molecular mechanisms of miR-324-3p regulating cardiac fibroblasts during AF remains unknown. In the present study, miR-324-3p was found to be decreased in patients with AF and AF rat model. Next, we investigated the effect of miR-324-3p on myocardial fibroblast proliferation through miR-324-3p overexpression and found that miR-324-3p inhibited fibroblast proliferation in vitro. Furthermore, we found that miR-324-3p directly targeted transforming growth factor β1 in fibroblast, which may be involved in the development of myocardial fibrosis during AF. Meanwhile, miR-324-3p mimics treatment suppressed the PI3K/AKT signaling pathway in fibroblast. These results demonstrated a molecular mechanism of miR-324-3p regulating fibroblast proliferation in vitro, which might provide a novel potential treatment manner in AF in clinic.

Keywords: Arrhythmias; Fibrosis; PI3K/AKT signaling; Rat model.

MeSH terms

  • Animals
  • Atrial Fibrillation / genetics*
  • Atrial Fibrillation / metabolism
  • Case-Control Studies
  • Cell Proliferation / genetics*
  • Disease Models, Animal
  • Exosomes / metabolism
  • Exosomes / ultrastructure
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Fibrosis
  • Humans
  • In Vitro Techniques
  • MicroRNAs / genetics*
  • Microscopy, Electron, Transmission
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, RNA
  • Signal Transduction
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • MIRN324 microRNA, rat
  • MicroRNAs
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta1
  • Proto-Oncogene Proteins c-akt