HIF1 transcription factor regulates laminin-332 expression and keratinocyte migration

被引:48
作者
Fitsialos, Giorgos [1 ,2 ]
Bourget, Isabelle [1 ,2 ]
Augier, Severine [1 ,2 ]
Ginouves, Amandine [3 ]
Rezzonico, Roger [1 ,2 ]
Odorisio, Teresa [4 ]
Cianfarani, Francesca [4 ]
Virolle, Thierry [1 ,2 ]
Pouyssegur, Jacques [3 ]
Meneguzzi, Guerrino [1 ,2 ]
Berra, Edurne [3 ,5 ]
Ponzio, Gilles [1 ,2 ]
Busca, Roser [1 ,2 ]
机构
[1] INSERM, U634, F-06107 Nice, France
[2] Univ Nice Sophia Antipolis, Fac Med, F-06000 Nice, France
[3] Ctr Antoine Lacassagne, CNRS, UMR 6543, F-06189 Nice, France
[4] IDI IRCCS, Mol & Cellular Biol Lab, I-00167 Rome, Italy
[5] CICbioGUNE, Cell Biol & Stem Cells Unit, Derio 48160, Spain
关键词
keratinocytes; HIF1; migration; laminin-332;
D O I
10.1242/jcs.029256
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:2992 / 3001
页数:10
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