title: Targeting hypoxia signalling for the treatment of ischaemic and inflammatory diseases.
abstract: Hypoxia-inducible factors (HIFs) are stabilized during adverse inflammatory processes associated with disorders such as inflammatory bowel disease, pathogen infection and acute lung injury, as well as during ischaemia-reperfusion injury. HIF stabilization and hypoxia-induced changes in gene expression have a profound impact on the inflamed tissue microenvironment and on disease outcomes. Although the mechanism that initiates HIF stabilization may vary, the final molecular steps that control HIF stabilization converge on a set of oxygen-sensing prolyl hydroxylases (PHDs) that mark HIFs for proteasomal degradation. PHDs are therefore promising therapeutic targets. In this Review, we discuss the emerging potential and associated challenges of targeting the PHD-HIF pathway for the treatment of inflammatory and ischaemic diseases.
authors.affiliation: Organ Protection Program, Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
authors.forename: Holger K
authors.initials: HK
authors.lastname: Eltzschig
authors.affiliation: Department of Pediatrics, National Jewish Health, Denver, Colorado 80206, USA.
authors.forename: Donna L
authors.initials: DL
authors.lastname: Bratton
authors.affiliation: Mucosal Inflammation Program, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Colgan
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D064828:Prolyl Hydroxylases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004364:Pharmaceutical Preparations; D064828:Prolyl Hydroxylases