title: Hypoxia and hypoxia-inducible factor in the burn wound.
abstract: The importance of hypoxia-inducible factor (HIF) in promoting angiogenesis and vasculogenesis during wound healing has been demonstrated. It is widely accepted that HIF activity can be promoted by many factors, including hypoxia in the wound or cytokines from inflammatory cells infiltrating the wound. However, there has not been a systematic exploration of the relationship between HIF activity and hypoxia in the burn wound. The location of the hypoxic tissue has not been clearly delineated. The time course of the appearance of hypoxia and the increased activity of HIF and appearance of HIF's downstream transcription products has not been described. The aim of this study was to utilize pimonidazole, a specific tissue hypoxia marker, to characterize the spatial and temporal course of hypoxia in a murine burn model and correlate this with the appearance of HIF-1α and its important angiogenic and vasculogenic transcription products vascular endothelial growth factor and SDF-1. Hypoxia was found in the healing margin of burn wounds beginning at 48 hours after burn and peaking at day 3 after burn. On sequential sections of the same tissue block, positive staining of HIF-1α, SDF-1, and vascular endothelial growth factor all occurred at the leading margin of the healing area and peaked at day 3, as did hypoxia. Immunohistochemical analysis was used to explore the characteristics of the hypoxic region of the wound. The localization of hypoxia was found to be related to cell growth and migration, but not to proliferation or inflammatory infiltration.
authors.affiliation: Hendrix Burn/Wound Laboratory, Section of Surgical Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Xing
authors.forename: Lixin
authors.initials: L
authors.lastname: Liu
authors.forename: Guy P
authors.initials: GP
authors.lastname: Marti
authors.forename: Xianjie
authors.initials: X
authors.lastname: Zhang
authors.forename: Maura
authors.initials: M
authors.lastname: Reinblatt
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Milner
authors.forename: John W
authors.initials: JW
authors.lastname: Harmon
mesh_terms: D000818:Animals; D002056:Burns / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015820:Cadherins / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D019610:Cytoprotection; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D046228:Microarray Analysis; D018919:Neovascularization, Physiologic; D009504:Neutrophils / Q000473:pathology; D009593:Nitroimidazoles; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
chemical_list: D015820:Cadherins; D054377:Chemokine CXCL12; D018925:Chemokines; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C118917:Krt17 protein, mouse; D009593:Nitroimidazoles; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C033815:pimonidazole; D007633:Keratins