Regulation of fibroblast migration by tenascin-C.

Journal article

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: Trebaul, A; Chan, E; Midwood, K

• Publication status: Published
• Journal: Biochemical Society transactions
• Volume: 35
• Issue: Pt 4
• Pages: 695-697
• Publication date: 2007-08-01
• DOI: 10.1042/bst0350695
• EISSN: 1470-8752
• ISSN: 0300-5127
• Language: English
• Keywords: Humans; Wound Healing; Animals; Cell Movement; Tenascin; Fibroblasts