期刊
JOURNAL OF CELL SCIENCE
卷 121, 期 18, 页码 2992-3001出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.029256
关键词
keratinocytes; HIF1; migration; laminin-332
类别
资金
- INSERM (Institut National de la Sante et la Recherche Medicale)
- ARC (Association pour la Recherche contre le Cancer) [3903]
- SFD (Societe Francaise de Dermatologie)
Epidermal wound repair is a complex process involving the fine orchestrated regulation of crucial cell functions, such as proliferation, adhesion and migration. Using an in vitro model that recapitulates central aspects of epidermal wound healing, we demonstrate that the transcription factor HIF1 is strongly stimulated in keratinocyte cultures submitted to mechanical injury. Signals generated by scratch wounding stabilise the HIF1 alpha protein, which requires activation of the PI3K pathway independently of oxygen availability. We further show that upregulation of HIF1 alpha plays an essential role in keratinocyte migration during the in vitro healing process, because HIF1 alpha inhibition dramatically delays the wound closure. In this context, we demonstrate that HIF1 controls the expression of laminin-332, one of the major epithelial cell adhesion ligands involved in cell migration and invasion. Indeed, silencing of HIF1 alpha abrogates injury-induced laminin-332 expression, and we provide evidence that HIF1 directly regulates the promoter activity of the laminin alpha 3 chain. Our results suggest that HIF1 contributes to keratinocyte migration and thus to the re-epithelialisation process by regulating laminin-332.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据