Reynolds, LE and Conti, FJ and Silva, R and Robinson, SD and Iyer, V and Rudling, R and Cross, B and Nye, E and Hart, IR and Dipersio, CM and Hodivala-Dilke, KM (2008) alpha3beta1 integrin-controlled Smad7 regulates reepithelialization during wound healing in mice. J Clin Invest , 118 (3) 965 - 974. 10.1172/JCI33538.
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Effective reepithelialization after injury is essential for correct wound healing. The upregulation of keratinocyte alpha3beta1 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-beta1-mediated responses. Specifically, expression of the inhibitor of TGF-beta1-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 alpha3beta1 integrin as a mediator of keratinocyte migration is not essential for reepithelialization but suggest instead that alpha3beta1 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.
|Title:||alpha3beta1 integrin-controlled Smad7 regulates reepithelialization during wound healing in mice.|
|Additional information:||PMCID: PMC2215730|
|Keywords:||Animals, Epithelium, Integrin alpha3beta1, Integrin alpha5beta1, Mice, Signal Transduction, Smad7 Protein, Transforming Growth Factor beta1, Wound Healing|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Child Health > Department of Neurosciences and Mental Health > ICH - Dubowitz Neuromuscular Centre|
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