miR-877-3p targets Smad7 and is associated with myofibroblast differentiation and bleomycin-induced lung fibrosis

Sci Rep. 2016 Jul 22:6:30122. doi: 10.1038/srep30122.

Abstract

Myofibroblast differentiation of lung resident mesenchymal stem cells (LR-MSC) plays an important role in idiopathic pulmonary fibrosis. By comparing the expression profiles of miRNAs before and after myofibroblast differentiation of LR-MSC, we identified miR-877-3p as a fibrosis-related miRNA. We found that miR-877-3p sequestration inhibited the myofibroblast differentiation of LR-MSC and attenuates bleomycin-induced lung fibrosis by targeting Smad7. Smad7, as an inhibitory smad in the TGF-β1 signaling pathway, was decreased in the myofibroblast differentiation of LR-MSC and up-regulation of Smad7 could inhibit the differentiation process. Our data implicates a potential application of miR-877-3p as a fibrosis suppressor for pulmonary fibrosis therapy and also as a fibrosis marker for predicting prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bleomycin / pharmacology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / physiology
  • Idiopathic Pulmonary Fibrosis / chemically induced
  • Idiopathic Pulmonary Fibrosis / metabolism*
  • Idiopathic Pulmonary Fibrosis / physiopathology*
  • Lung / drug effects
  • Lung / metabolism
  • Male
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*
  • Myofibroblasts / metabolism*
  • Myofibroblasts / physiology*
  • Signal Transduction / physiology
  • Smad7 Protein / metabolism*
  • Transforming Growth Factor beta1 / metabolism
  • Up-Regulation / physiology

Substances

  • MIRN877 microRNA, human
  • MicroRNAs
  • SMAD7 protein, human
  • Smad7 Protein
  • Transforming Growth Factor beta1
  • Bleomycin