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Activation of Transforming Growth Factor- by the Integrin v8 Delays Epithelial Wound Closure

Department of Medicine, and Department of Pathology, Lung Biology Center, University of California, San Francisco, California

Correspondence and requests for reprints should be addressed to Dean Sheppard, Lung Biology Center, University of California, San Francisco, Box 2922, San Francisco, CA 94143-2922. E-mail: dean.sheppard{at}ucsf.edu

Transforming growth factor (TGF)- family members regulate multiple aspects of wound repair through effects on cell proliferation, matrix production, and tissue inflammation, but the effects of TGF- on wound closure itself have been controversial. We found that blocking antibodies to TGF- enhanced the degree of closure of scratch wounds in primary airway epithelial monolayers, while addition of exogenous TGF-1 inhibited the degree of closure, suggesting that endogenous activation of TGF- normally serves as a brake on the degree of wound closure. Although these cells secreted large amounts of TGF-2 and small amounts of TGF-1, blockade of TGF-1 enhanced the degree of wound closure, whereas blockade of TGF-2 had no effect. TGF-1 (but not TGF-2) can be activated by two members of the integrin family, v6 and v8, which are both expressed on airway epithelial cells. Wounding induced activation of TGF- through effects of both integrins, but antibodies against v8 enhanced the degree of wound closure, whereas antibodies against v6 did not.

Key Words: airway epithelium • integrin v6 • integrin v8 • TGF- • wound closure

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