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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Bielefeld, KA; Amini-Nik, S; Whetstone, H; Poon, R; Youn, A; Wang, J; Alman, BA

Published Date

  • August 2011

Published In

Volume / Issue

  • 286 / 31

Start / End Page

  • 27687 - 27697

PubMed ID

  • 21652705

Pubmed Central ID

  • 21652705

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M111.261677

Language

  • eng