The small G protein Arf6 expressed in keratinocytes by HGF stimulation is a regulator for skin wound healing

Sci Rep. 2017 Apr 21:7:46649. doi: 10.1038/srep46649.


The earlier step of cutaneous wound healing process, re-epithelialization of the wounded skin, is triggered by a variety of growth factors. However, molecular mechanisms through which growth factors trigger skin wound healing are less understood. Here, we demonstrate that hepatocyte growth factor (HGF)/c-Met signaling-induced expression of the small G protein Arf6 mRNA in keratinocytes is essential for the skin wound healing. Arf6 mRNA expression was dramatically induced in keratinocytes at the wounded skin, which was specifically suppressed by the c-Met inhibitor. Wound healing of the skin was significantly delayed in keratinocyte-specific Arf6 conditional knockout mice. Furthermore, Arf6 deletion from keratinocytes remarkably suppressed HGF-stimulated cell migration and peripheral membrane ruffle formation, but did not affect skin morphology and proliferation/differentiation of keratinocytes. These results are consistent with the notion that Arf6 expressed in skin keratinocytes through the HGF/c-Met signaling pathway in response to skin wounding plays an important role in skin wound healing by regulating membrane dynamics-based motogenic cellular function of keratinocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factor 6
  • ADP-Ribosylation Factors / genetics
  • ADP-Ribosylation Factors / metabolism*
  • Animals
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / metabolism*
  • Keratinocytes / metabolism*
  • Keratinocytes / pathology
  • Mice
  • Mice, Knockout
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Signal Transduction*
  • Skin* / injuries
  • Skin* / metabolism
  • Skin* / pathology
  • Wound Healing*


  • ADP-Ribosylation Factor 6
  • HGF protein, mouse
  • Hepatocyte Growth Factor
  • RON protein
  • Receptor Protein-Tyrosine Kinases
  • ADP-Ribosylation Factors
  • ARF6 protein, human
  • Arf6 protein, mouse