Activation of Transforming Growth Factor-β by the Integrin αvβ8 Delays Epithelial Wound Closure

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Abstract
Transforming growth factor (TGF)-beta family members regulate multiple aspects of wound repair through effects on cell proliferation, matrix production, and tissue inflammation, but the effects of TGF-beta on wound closure itself have been controversial. We found that blocking antibodies to TGF-beta enhanced the degree of closure of scratch wounds in primary airway epithelial monolayers, while addition of exogenous TGF-beta1 inhibited the degree of closure, suggesting that endogenous activation of TGF-beta normally serves as a brake on the degree of wound closure. Although these cells secreted large amounts of TGF-beta2 and small amounts of TGF-beta1, blockade of TGF-beta1 enhanced the degree of wound closure, whereas blockade of TGF-beta2 had no effect. TGF-beta1 (but not TGF-beta2) can be activated by two members of the integrin family, alphavbeta6 and alphavbeta8, which are both expressed on airway epithelial cells. Wounding induced activation of TGF-beta through effects of both integrins, but antibodies against alphavbeta8 enhanced the degree of wound closure, whereas antibodies against alphavbeta6 did not.