α3β1 integrin-controlled Smad7 regulates reepithelialization during wound healing in mice

被引：82

作者：

Reynolds, Louise E. ^{[1
,2
,3
]}

Conti, Francesco J. ^{[4
]}

Silva, Rita ^{[1
,2
,3
]}

Robinson, Stephen D. ^{[1
,2
,3
]}

Iyer, Vandana ^{[5
]}

Rudling, Rob ^{[6
]}

Cross, Barbara ^{[6
]}

Nye, Emma ^{[6
]}

Hart, Ian R. ^{[1
,2
,3
]}

DiPersio, C. Michael ^{[5
]}

Hodivala-Dilke, Kairbaan M. ^{[1
,2
,3
]}

机构：

[1] Inst Canc Res, Tumor Biol Ctr, London EC1M 6BQ, England

[2] Canc Res UK Clin Ctr, London EC1M 6BQ, England

[3] John Vane Sci Ctr, Queen Marys Sch Med & Dent, London EC1M 6BQ, England

[4] Scripps Res Inst, La Jolla, CA USA

[5] Albany Med Coll, Ctr Cell Biol & Canc Res, Albany, NY 12208 USA

[6] Canc Res UK, London Res Inst, Expt Pathol Lab, London, England

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2008年 / 118卷 / 03期

关键词：

D O I：

10.1172/JCI33538

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Effective reepithelialization after injury is essential for correct wound healing. The upregulation of keratinocyte alpha 3 beta 1 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-beta 1-mediated responses. Specifically, expression of the inhibitor of TGF-beta 1-signaling Smad7 was elevated in Itga3(-/-) keratinocytes. Indeed, in vivo blockade of SmaA7 increased the rate of reepithelialization in Itga3(-/-) and WT wounds to similar levels. Our data therefore indicate that the function of alpha 3 beta 1 integrin as a mediator of keratinocyte migration is not essential for reepithelialization but suggest instead that alpha 3 beta 1 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.

引用

页码：965 / 974

页数：10

共 46 条

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