MicroRNA-132 promotes fibroblast migration via regulating RAS p21 protein activator 1 in skin wound healing

Sci Rep. 2017 Aug 10;7(1):7797. doi: 10.1038/s41598-017-07513-0.

Abstract

MicroRNA (miR)-132 has been identified as a top up-regulated miRNA during skin wound healing and its inhibition impairs wound repair. In a human in vivo surgical wound model, we showed that miR-132 was induced in epidermal as well as in dermal wound-edge compartments during healing. Moreover, in a panel of cells isolated from human skin wounds, miR-132 was found highly expressed in human dermal fibroblasts (HDFs). In HDFs, miR-132 expression was upregulated by TGF-β1. By overexpression or inhibition of miR-132, we showed that miR-132 promoted HDF migration. Mechanistically, global transcriptome analysis revealed that RAS signaling pathway was regulated by miR-132 in HDFs. We found that RAS p21 protein activator 1 (RASA1), a known target of miR-132, was downregulated in HDFs upon miR-132 overexpression. Silencing of RASA1 phenocopied the pro-migratory effect of miR-132. Collectively, our study reveals an important role for miR-132 in HDFs during wound healing and indicates a therapeutic potential of miR-132 in hard-to-heal skin wounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement
  • Cells, Cultured
  • Down-Regulation
  • Fibroblasts / chemistry
  • Fibroblasts / cytology*
  • Gene Expression Profiling / methods
  • Humans
  • MicroRNAs / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Signal Transduction
  • Surgical Wound / genetics*
  • Transforming Growth Factor beta1 / pharmacology
  • Up-Regulation
  • Wound Healing
  • p120 GTPase Activating Protein / genetics*

Substances

  • MIRN132 microRNA, human
  • MicroRNAs
  • RASA1 protein, human
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • p120 GTPase Activating Protein