Injury-activated glial cells promote wound healing of the adult skin in mice

Nat Commun. 2018 Jan 16;9(1):236. doi: 10.1038/s41467-017-01488-2.

Abstract

Cutaneous wound healing is a complex process that aims to re-establish the original structure of the skin and its functions. Among other disorders, peripheral neuropathies are known to severely impair wound healing capabilities of the skin, revealing the importance of skin innervation for proper repair. Here, we report that peripheral glia are crucially involved in this process. Using a mouse model of wound healing, combined with in vivo fate mapping, we show that injury activates peripheral glia by promoting de-differentiation, cell-cycle re-entry and dissemination of the cells into the wound bed. Moreover, injury-activated glia upregulate the expression of many secreted factors previously associated with wound healing and promote myofibroblast differentiation by paracrine modulation of TGF-β signalling. Accordingly, depletion of these cells impairs epithelial proliferation and wound closure through contraction, while their expansion promotes myofibroblast formation. Thus, injury-activated glia and/or their secretome might have therapeutic potential in human wound healing disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Gene Expression Profiling
  • Humans
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Knockout
  • Mice, Transgenic
  • Myofibroblasts / metabolism
  • Myofibroblasts / physiology
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • Neuroglia / physiology*
  • SOXE Transcription Factors / genetics
  • SOXE Transcription Factors / metabolism
  • Signal Transduction / genetics
  • Skin / injuries
  • Skin / innervation
  • Skin / physiopathology*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Wound Healing / genetics
  • Wound Healing / physiology*

Substances

  • SOXE Transcription Factors
  • Sox10 protein, mouse
  • Transforming Growth Factor beta