title: HIF1 transcription factor regulates laminin-332 expression and keratinocyte migration.
abstract: 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 HIF1alpha protein, which requires activation of the PI3K pathway independently of oxygen availability. We further show that upregulation of HIF1alpha plays an essential role in keratinocyte migration during the in vitro healing process, because HIF1alpha 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 HIF1alpha abrogates injury-induced laminin-332 expression, and we provide evidence that HIF1 directly regulates the promoter activity of the laminin alpha3 chain. Our results suggest that HIF1 contributes to keratinocyte migration and thus to the re-epithelialisation process by regulating laminin-332.
authors: INSERM U634, F-06107 Nice, France.
authors: Giorgos
authors: G
authors: Fitsialos
authors: Isabelle
authors: I
authors: Bourget
authors: Séverine
authors: S
authors: Augier
authors: Amandine
authors: A
authors: Ginouvès
authors: Roger
authors: R
authors: Rezzonico
authors: Teresa
authors: T
authors: Odorisio
authors: Francesca
authors: F
authors: Cianfarani
authors: Thierry
authors: T
authors: Virolle
authors: Jacques
authors: J
authors: Pouysségur
authors: Guerrino
authors: G
authors: Meneguzzi
authors: Edurne
authors: E
authors: Berra
authors: Gilles
authors: G
authors: Ponzio
authors: Roser
authors: R
authors: Buscà
mesh_terms: D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000502:physiology; D014945:Wound Healing; D000097794:Kalinin
chemical_list: D015815:Cell Adhesion Molecules; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007797:Laminin; D019869:Phosphatidylinositol 3-Kinases; D000097794:Kalinin; C095567:laminin alpha 3