title: Regulation of fibroblast migration by tenascin-C.
abstract: Synthesis of new tissue by fibroblasts is required for tissue rebuilding in response to injury. Fibroblast migration from surrounding healthy tissue into the fibrin-fibronectin provisional matrix deposited upon injury is a key rate-limiting step of this stage of tissue repair. These events must be tightly regulated. Excessive deposition of scar tissue is the major hallmark of fibrotic disease. Tenascin-C is an extracellular matrix glycoprotein that is transiently expressed upon tissue injury, where it is specifically localized to the wound edge, and persistently up-regulated in fibrotic disease. We have shown that full-length tenascin-C promotes fibroblast migration within fibrin-fibronectin matrices and we have mapped the domains within the molecule critical for enhancing migration. We also demonstrated that specific fragments of tenascin-C inhibit fibroblast migration. These results suggest that transient expression of tenascin-C at the wound boundary is key to tissue repair: its induction recruits fibroblasts into the wound and fragments resulting from its breakdown prevent excessive fibroblast infiltration. Our results demonstrate how fibroblast migration in three-dimensional provisional matrices may be differentially regulated by proteolysis of matrix molecules and could explain how persistent expression of tenascin-C contributes to the progression of fibrotic disease.
authors.affiliation: Kennedy Institute of Rheumatology, Imperial College London, 1 Aspenlea Road, London W6 8LH, UK.
authors.forename: A
authors.initials: A
authors.lastname: Trebaul
authors.forename: E K
authors.initials: EK
authors.lastname: Chan
authors.forename: K S
authors.initials: KS
authors.lastname: Midwood
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D019063:Tenascin / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D019063:Tenascin