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

ABSTRACT: ?-Catenin is an important regulator of dermal fibroblasts during cutaneous wound repair. However, the factors that modulate ?-catenin activity in this process are not completely understood. We investigated the role of the extracellular matrix in regulating ?-catenin and found an increase in ?-catenin-mediated Tcf-dependent transcriptional activity in fibroblasts exposed to various extracellular matrix components. This occurs through an integrin-mediated GSK3?-dependent pathway. The physiologic role of this mechanism was demonstrated during wound repair in extra domain A-fibronectin-deficient mice, which exhibited decreased ?-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 ?-catenin signaling. Because fibronectin is a transcriptional target of ?-catenin, this suggests the existence of a feedback loop between these two molecules that regulates dermal fibroblast cell behavior during wound repair.

SUBMITTER: Bielefeld KA 

PROVIDER: S-EPMC3149359 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature