Louise E. Reynolds, Francesco J. Conti, Rita Silva, Stephen D. Robinson, Vandana Iyer, Rob Rudling, Barbara Cross, Emma Nye, Ian R. Hart, C. Michael DiPersio, Kairbaan M. Hodivala-Dilke
J Clin Invest.
2008;
118(3):965–974
doi:10.1172/JCI33538
This article Copyright © 2008, The American Society for Clinical Investigation
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E
ffective reepithelialization after injury is essential for correct wound healing. The upregulation of keratinocyte α3β1 integrin during reepithelialization suggests that this adhesion molecule is involved in wound healing; however, its precise role in this process is unknown. We have shown here that retarded reepithelialization in Itga3–/– mouse skin wounds is due predominantly to repressed TGF-β1–mediated responses. Specifically, expression of the inhibitor of TGF-β1–signaling Smad7 was elevated in Itga3–/– keratinocytes. Indeed, in vivo blockade of Smad7 increased the rate of reepithelialization in Itga3–/– and WT wounds to similar levels. Our data therefore indicate that the function of α3β1 integrin as a mediator of keratinocyte migration is not essential for reepithelialization but suggest instead that α3β1 integrin has a major new in vivo role as an inhibitor of Smad7 during wound healing. Moreover, our study may identify a previously undocumented function for Smad7 as a regulator of reepithelialization in vivo and implicates Smad7 as a potential novel target for the treatment of cutaneous wounds.
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