Injury triggers fascia fibroblast collective cell migration to drive scar formation through N-cadherin

Nat Commun. 2020 Nov 6;11(1):5653. doi: 10.1038/s41467-020-19425-1.

Abstract

Scars are more severe when the subcutaneous fascia beneath the dermis is injured upon surgical or traumatic wounding. Here, we present a detailed analysis of fascia cell mobilisation by using deep tissue intravital live imaging of acute surgical wounds, fibroblast lineage-specific transgenic mice, and skin-fascia explants (scar-like tissue in a dish - SCAD). We observe that injury triggers a swarming-like collective cell migration of fascia fibroblasts that progressively contracts the skin and form scars. Swarming is exclusive to fascia fibroblasts, and requires the upregulation of N-cadherin. Both swarming and N-cadherin expression are absent from fibroblasts in the upper skin layers and the oral mucosa, tissues that repair wounds with minimal scar. Impeding N-cadherin binding inhibits swarming and skin contraction, and leads to reduced scarring in SCADs and in animals. Fibroblast swarming and N-cadherin thus provide therapeutic avenues to curtail fascia mobilisation and pathological fibrotic responses across a range of medical settings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Cadherins / metabolism
  • Cell Movement
  • Cicatrix / metabolism*
  • Cicatrix / physiopathology
  • Fascia / cytology
  • Fascia / injuries*
  • Fascia / metabolism
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Skin / cytology
  • Skin / injuries
  • Skin / metabolism
  • Skin / physiopathology
  • Wound Healing
  • Wounds and Injuries / metabolism*
  • Wounds and Injuries / physiopathology
  • Young Adult

Substances

  • Cadherins