Fibronectin and beta-catenin act in a regulatory loop in dermal fibroblasts to modulate cutaneous healing

J Biol Chem. 2011 Aug 5;286(31):27687-97. doi: 10.1074/jbc.M111.261677. Epub 2011 Jun 7.


β-Catenin is an important regulator of dermal fibroblasts during cutaneous wound repair. However, the factors that modulate β-catenin activity in this process are not completely understood. We investigated the role of the extracellular matrix in regulating β-catenin and found an increase in β-catenin-mediated Tcf-dependent transcriptional activity in fibroblasts exposed to various extracellular matrix components. This occurs through an integrin-mediated GSK3β-dependent pathway. The physiologic role of this mechanism was demonstrated during wound repair in extra domain A-fibronectin-deficient mice, which exhibited decreased β-catenin-mediated signaling during the proliferative phase of healing. Extra domain A-fibronectin-deficient mice have wounds that fail at a lower tensile strength and contain fewer fibroblasts compared with wild type mice. This phenotype was rescued by genetic or pharmacologic activation of β-catenin signaling. Because fibronectin is a transcriptional target of β-catenin, this suggests the existence of a feedback loop between these two molecules that regulates dermal fibroblast cell behavior during wound repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fibroblasts / cytology
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Fibronectins / physiology*
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Immunohistochemistry
  • Mice
  • Mice, Knockout
  • Signal Transduction
  • Skin / cytology*
  • Wound Healing / physiology*
  • beta Catenin / metabolism
  • beta Catenin / physiology*


  • Fibronectins
  • beta Catenin
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Glycogen Synthase Kinase 3