alpha3beta1 integrin-controlled Smad7 regulates reepithelialization during wound healing in mice.
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.
Reynolds
Louise E
LE
Centre for Tumour Biology, Institute of Cancer Research and Cancer Research UK Clinical Centre, Barts and The London, Queen Mary's School of Medicine and Dentistry, John Vane Science Centre, London, United Kingdom.
Conti
Francesco J
FJ
Silva
Rita
R
Robinson
Stephen D
SD
Iyer
Vandana
V
Rudling
Rob
R
Cross
Barbara
B
Nye
Emma
E
Hart
Ian R
IR
Dipersio
C Michael
CM
Hodivala-Dilke
Kairbaan M
KM
D000818:Animals; D004848:Epithelium / Q000502:physiology*; D039201:Integrin alpha3beta1 / Q000502:physiology*; D039081:Integrin alpha5beta1 / Q000502:physiology; D051379:Mice; D015398:Signal Transduction; D051906:Smad7 Protein / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D014945:Wound Healing
D039201:Integrin alpha3beta1; D039081:Integrin alpha5beta1; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D053773:Transforming Growth Factor beta1