title: Hypoxia signaling during acute lung injury.
abstract: Acute lung injury (ALI) is an inflammatory lung disease that manifests itself in patients as acute respiratory distress syndrome and thereby contributes significantly to the morbidity and mortality of patients experiencing critical illness. Even though it may seem counterintuitive, as the lungs are typically well-oxygenated organs, hypoxia signaling pathways have recently been implicated in the resolution of ALI. For example, functional studies suggest that transcriptional responses under the control of the hypoxia-inducible factor (HIF) are critical in optimizing alveolar epithelial carbohydrate metabolism, and thereby dampen lung inflammation during ALI. In the present review we discuss functional roles of oxygenation, hypoxia and HIFs during ALI, mechanisms of how HIFs are stabilized during lung inflammation, and how HIFs can mediate lung protection during ALI.
authors.affiliation: Organ Protection Program, Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado; Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado; and christine.vohwinkel@ucdenver.edu.
authors.forename: Christine U
authors.initials: CU
authors.lastname: Vohwinkel
authors.affiliation: Organ Protection Program, Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado; Department of Anesthesiology, University Hospital, Ludwig Maximilian University, Munich, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hoegl
authors.affiliation: Organ Protection Program, Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado;
authors.forename: Holger K
authors.initials: HK
authors.lastname: Eltzschig
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism*; D000818:Animals; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018836:Inflammation Mediators
keywords: HIF1A; LPS; acute lung injury; acute respiratory distress syndrome; carbohydrate metabolism; glycolysis; hypoxia; hypoxia-inducible factor; inflammation; lung protection; mechanical ventilation; sepsis