MicroRNA-31 Promotes Skin Wound Healing by Enhancing Keratinocyte Proliferation and Migration

J Invest Dermatol. 2015 Jun;135(6):1676-1685. doi: 10.1038/jid.2015.48. Epub 2015 Feb 16.


Wound healing is a basic biological process restoring the integrity of the skin. The role of microRNAs during this process remains largely unexplored. By using an in vivo human skin wound healing model, we show here that the expression of miR-31 is gradually upregulated in wound edge keratinocytes in the inflammatory (1 day after injury) through the proliferative phase (7 days after injury) in comparison with intact skin. In human primary keratinocytes, overexpression of miR-31 promoted cell proliferation and migration, whereas inhibition of miR-31 had the opposite effects. Moreover, we identified epithelial membrane protein 1 (EMP-1) as a direct target of miR-31 in keratinocytes. The expression of EMP-1 in the skin was negatively correlated with the level of miR-31 during wound healing. Silencing of EMP-1 mimicked the effects of overexpression of miR-31 on keratinocyte proliferation and migration, indicating that EMP-1 is a critical target mediating the functions of miR-31 in keratinocytes. Finally, we demonstrated that transforming growth factor-β2, which is highly expressed in skin wounds, upregulated miR-31 expression in keratinocytes. Collectively, we identify miR-31 as a key regulator for promoting keratinocyte proliferation and migration during wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biopsy
  • Cell Movement
  • Cell Proliferation*
  • Cells, Cultured
  • Female
  • Gene Expression Regulation
  • Gene Silencing
  • Humans
  • Inflammation
  • Keratinocytes / cytology*
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Proteins / metabolism
  • Receptors, Cell Surface / metabolism
  • Skin / metabolism*
  • Transforming Growth Factor beta2 / metabolism
  • Up-Regulation
  • Wound Healing*
  • Young Adult


  • MIRN31 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • Receptors, Cell Surface
  • Transforming Growth Factor beta2
  • epithelial membrane protein-1