title: Reduced up-regulation of cytoprotective genes in rat cutaneous tissue during the second cycle of ischemia-reperfusion.
abstract: Chronic wounds are major health problems that affect millions of people in the United States every year. Management of these wounds costs billions of dollars annually in the United States. Despite their clinical importance, the molecular mechanisms underlying these clinical conditions remain elusive. Repetitive ischemia-reperfusion (I-R) may play a pivotal role in chronic wound formation. The development of therapies for these wounds is hindered by the lack of animal models that allow identification of the molecular mechanisms underlying chronic wound formation. In the first study of its kind, we adapted our rat pressure sore model by imposing two cycles of ischemia (2 hours) and two cycles of reperfusion (24 hours), and we examined gene expression to better understand the molecular events that occur at the very early stages of cutaneous I-R injury with a goal of devising preventing strategies. We successfully tested our hypothesis and demonstrated that while cytoprotective genes, such as heat shock protein 70, heat shock protein 90, hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and heme oxygenase-1, were initially up-regulated during the first cycle of I-R, their up-regulation was subsequently reduced or completely abolished during the second cycle of I-R. These findings raise the possibility that reduced up-regulation of these cytoprotective genes may be causally linked to cutaneous I-R injury.
authors.affiliation: Wound Healing Research Laboratory, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Sisco
authors.forename: W Robert
authors.initials: WR
authors.lastname: Liu
authors.forename: Zol B
authors.initials: ZB
authors.lastname: Kryger
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Mustoe
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002908:Chronic Disease; D005786:Gene Expression Regulation / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D018841:HSP90 Heat-Shock Proteins / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000502:physiology; D051793:Hypoxia-Inducible Factor 1 / Q000502:physiology; D016133:Polymerase Chain Reaction; D003668:Pressure Ulcer / Q000235:genetics / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics / Q000503:physiopathology*; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D051793:Hypoxia-Inducible Factor 1; D042461:Vascular Endothelial Growth Factor A; D051547:Heme Oxygenase-1