MiR-155 Knockout in Fibroblasts Improves Cardiac Remodeling by Targeting Tumor Protein p53-Inducible Nuclear Protein 1

J Cardiovasc Pharmacol Ther. 2016 Jul;21(4):423-35. doi: 10.1177/1074248415616188. Epub 2015 Nov 20.

Abstract

Cardiac remodeling caused by acute myocardial infarction (AMI) represents a major challenge for heart failure research. MiR-155 has been identified as a key mediator of cardiac inflammation and hypertrophy. In this study, we investigate the role of miR-155 in cardiac remodeling induced by AMI. We demonstrate that miR-155 expressed in cardiac fibroblasts is a potent contributor to cardiac remodeling. We reveal that in vivo, miR-155 knockout improves left ventricular function, reduces infarct size, and attenuates collagen deposition, whereas overexpression of miR-155 produces the opposite effects. MiR-155 knockout also inhibits cardiac fibroblast proliferation and differentiation into myofibroblasts. In addition, downregulation of tumor protein p53-inducible nuclear protein 1 (TP53INP1) by small interfering RNA reverses the effects of miR-155 knockout on cardiac fibroblasts. Our data reveal that knockout of miR-155 in cardiac fibroblasts improves cardiac remodeling by targeting TP53INP1, which may be a novel treatment strategy for cardiac remodeling.

Keywords: acute myocardial infarction; cardiac remodeling; fibroblast; microRNA; tumor protein p53-inducible nuclear protein 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Collagen / metabolism
  • Disease Models, Animal
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Gene Expression Regulation
  • Genotype
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Myocardial Infarction / genetics
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Myofibroblasts / metabolism
  • Myofibroblasts / pathology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phenotype
  • RNA Interference
  • Signal Transduction
  • Time Factors
  • Transfection
  • Ventricular Function, Left*
  • Ventricular Remodeling*

Substances

  • MicroRNAs
  • Mirn155 microRNA, mouse
  • Nuclear Proteins
  • tumor protein 53-induced nuclear protein 1, mouse
  • Collagen