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First published online 19 August 2008
doi: 10.1242/jcs.029256

Journal of Cell Science 121, 2992-3001 (2008)
Published by The Company of Biologists 2008
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Research Article

HIF1 transcription factor regulates laminin-332 expression and keratinocyte migration

Giorgos Fitsialos1,2,*, Isabelle Bourget1,2,*, Séverine Augier1,2, Amandine Ginouvès3, Roger Rezzonico1,2, Teresa Odorisio4, Francesca Cianfarani4, Thierry Virolle1,2, Jacques Pouysségur3, Guerrino Meneguzzi1,2, Edurne Berra3,5, Gilles Ponzio1,2,{ddagger} and Roser Buscà1,2

1 INSERM U634, 28 avenue de Valombrose, F-06107 Nice, France
2 Université de Nice Sophia Antipolis, Faculté de Médecine, F-06000 Nice, France
3 CNRS UMR 6543, Centre Antoine Lacassagne, 33, avenue de Valombrose, 06189 Nice, France
4 Laboratory of Molecular and Cellular Biology, IDI-IRCCS, via Monti di Creta, 104 00167 Roma, Italy
5 CICbioGUNE, Cell Biology and Stem Cells Unit, Technologic Park of Bizkaia, 48160 Derio, Spain

{ddagger} Author for correspondence (e-mail: ponzio{at}unice.fr)

Accepted 16 June 2008

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.

Key words: Keratinocytes, HIF1, Migration, Laminin-332


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