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First published online September 3, 2008

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How HIF1 helps healing

The transcription factor hypoxia-inducible factor 1 (HIF1), which regulates oxygen homeostasis, is activated by stabilisation of the HIF1 subunit under low-oxygen conditions. Several studies have hinted that HIF1 might also have a role in cell adhesion and motility; now, Roser Buscà and colleagues (p. 2992) establish that HIF1 is important in keratinocyte migration during wound healing. The authors previously used an in vitro scratch-wound assay to show that several targets of HIF1 were upregulated in keratinocyte sheets in response to wounding, and they now show that HIF1 protein levels increase under the same conditions. Moreover, they demonstrate that HIF1 stabilisation is regulated by the PI3K-Akt pathway and, unusually, occurs under normoxic conditions. When HIF1 is depleted by siRNA, keratinocyte migration is impaired; additionally, HIF1 depletion abolishes the scratch-wound-dependent upregulation of the ECM protein laminin-332 (which is important in wound healing). The authors show that HIF1 binds directly to the promoter region of LAMA3 (which encodes the -subunit of laminin-332) and stimulates LAMA3 transcription. Their results shed light on the mechanism of wound healing and establish a new, hypoxia-independent role for HIF1.

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Related articles in JCS:

HIF1 transcription factor regulates laminin-332 expression and keratinocyte migration

Giorgos Fitsialos, Isabelle Bourget, Séverine Augier, Amandine Ginouvès, Roger Rezzonico, Teresa Odorisio, Francesca Cianfarani, Thierry Virolle, Jacques Pouysségur, Guerrino Meneguzzi, Edurne Berra, Gilles Ponzio, and Roser Buscà
JCS 2008 121: 2992-3001. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?