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.
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Conference Article|
July 20 2007
Regulation of fibroblast migration by tenascin-C
A. Trebaul;
A. Trebaul
1Kennedy Institute of Rheumatology, Imperial College London, 1 Aspenlea Road, London W6 8LH, U.K.
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E.K. Chan;
E.K. Chan
1Kennedy Institute of Rheumatology, Imperial College London, 1 Aspenlea Road, London W6 8LH, U.K.
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K.S. Midwood
K.S. Midwood
1
1Kennedy Institute of Rheumatology, Imperial College London, 1 Aspenlea Road, London W6 8LH, U.K.
1To whom correspondence should be addressed (email k.midwood@imperial.ac.uk).
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Publisher: Portland Press Ltd
Received:
March 30 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem Soc Trans (2007) 35 (4): 695–697.
Article history
Received:
March 30 2007
Citation
A. Trebaul, E.K. Chan, K.S. Midwood; Regulation of fibroblast migration by tenascin-C. Biochem Soc Trans 1 August 2007; 35 (4): 695–697. doi: https://doi.org/10.1042/BST0350695
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