Activation of transforming growth factor-β by the integrin αvβ8 delays epithelial wound closure

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-beta 1 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-beta 2 and small amounts of TGF-beta 1, blockade of TGF-beta 1 enhanced the degree of wound closure, whereas blockade of TGF-beta 2 had no effect. TGF-beta 1 (but not TGF-beta 2) can be activated by two members of the integrin family, alpha v beta 6 and alpha v beta 8, which are both expressed on airway epithelial cells. Wounding induced activation of TGF-beta through effects of both integrins, but antibodies against alpha v beta 8 enhanced the degree of wound closure, whereas antibodies against alpha v beta 6 did not.