Submitted on January 10, 2006
Revised on March 28, 2006
Activation of Transforming Growth Factor-
by the Integrin 
v8 Delays Epithelial Wound Closure
Claus Neurohr1, Stephen L Nishimura2, and Dean Sheppard1*
1 Department of Medicine, Lung Biology Center, University of California, San Francisco, San Francisco, California, USA,
2 Department of Pathology, Lung Biology Center, University of California, San Francisco, San Francisco, California, USA
* To whom correspondence should be addressed. 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 TGF1 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 TGF2 and small amounts of TGF1, blockade of TGF1 enhanced the degree of wound closure, whereas blockade of TGF2 had no effect. TGF1 (but not TGF2) 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.
