title: Epidermal deletion of HIF-2α stimulates wound closure.
abstract: Wound closure requires a complex series of micro-environmentally influenced events. A key aspect of wound closure is the migration of keratinocytes across the open wound. It has been found previously that the response to hypoxia via the HIF-1α transcription factor is a key feature of wound closure. The need for hypoxic response is likely due to interrupted wound vasculature, as well as infection, and in this work we investigated the need for a highly related hypoxic response transcription factor, HIF-2α. This factor was deleted tissue specifically in mice, and the resulting mice were found to have an accelerated rate of wound closure. This is correlated with a reduced bacterial load and inflammatory response in these mice. This indicates that manipulating or reducing the HIF-2α response in keratinocytes could be a useful means to accelerate wound healing and tissue repair.
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Cowburn
authors.affiliation: Pulmonary & Critical Care Section, VA San Diego Healthcare System, La Jolla, California, USA.
authors.forename: Laura E Crotty
authors.initials: LEC
authors.lastname: Alexander
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Southwood
authors.affiliation: Division of Pediatric Pharmacology and Drug Discovery, UCSD School of Medicine, La Jolla, California, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Chilvers
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK. Electronic address: rsj33@cam.ac.uk.
authors.forename: Randall S
authors.initials: RS
authors.lastname: Johnson
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D002461:Cell Line, Transformed; D003872:Dermatitis / Q000473:pathology / Q000503:physiopathology; D000078404:Epidermal Cells; D004817:Epidermis / Q000293:injuries / Q000502:physiology*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D000099162:Endothelial PAS Domain-Containing Protein 1; C494469:VHL protein, mouse
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