title: Fibronectin and beta-catenin act in a regulatory loop in dermal fibroblasts to modulate cutaneous healing.
abstract: 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.
authors.affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children Research Institute, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Bielefeld
authors.forename: Saeid
authors.initials: S
authors.lastname: Amini-Nik
authors.forename: Heather
authors.initials: H
authors.lastname: Whetstone
authors.forename: Raymond
authors.initials: R
authors.lastname: Poon
authors.forename: Andrew
authors.initials: A
authors.lastname: Youn
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Alman
mesh_terms: D000818:Animals; D005347:Fibroblasts / Q000166:cytology; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction; D012867:Skin / Q000166:cytology*; D014945:Wound Healing / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism / Q000502:physiology*
chemical_list: D005353:Fibronectins; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3