Hypoxia-inducible factors as molecular targets for liver diseases.
Liver disease is a growing global health problem, as deaths from end-stage liver cirrhosis and cancer are rising across the world. At present, pharmacologic approaches to effectively treat or prevent liver disease are extremely limited. Hypoxia-inducible factor (HIF) is a transcription factor that regulates diverse signaling pathways enabling adaptive cellular responses to perturbations of the tissue microenvironment. HIF activation through hypoxia-dependent and hypoxia-independent signals have been reported in liver disease of diverse etiologies, from ischemia-reperfusion-induced acute liver injury to chronic liver diseases caused by viral infection, excessive alcohol consumption, or metabolic disorders. This review summarizes the evidence for HIF stabilization in liver disease, discusses the mechanistic involvement of HIFs in disease development, and explores the potential of pharmacological HIF modifiers in the treatment of liver disease.
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy, University of Colorado, Auroa, Colorado, 800045, USA. cynthia.ju@ucdenver.edu.
Cynthia
C
Ju
Department of Medicine and Mucosal Inflammation Program, School of Medicine, University of Colorado, Auroa, Colorado, 800045, USA.
Sean P
SP
Colgan
Department of Anesthesiology and Organ Protection Program, School of Medicine, University of Colorado, Auroa, Colorado, 800045, USA.
Holger K
HK
Eltzschig
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000068258:Bevacizumab / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002986:Clinical Trials as Topic; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D005786:Gene Expression Regulation; D006525:Hepatitis, Viral, Human / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008108:Liver Diseases, Alcoholic / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D058990:Molecular Targeted Therapy; D009841:Oligonucleotides / Q000627:therapeutic use; D015398:Signal Transduction; D000099162:Endothelial PAS Domain-Containing Protein 1
D000970:Antineoplastic Agents; D051792:Basic Helix-Loop-Helix Proteins; D000068258:Bevacizumab; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009841:Oligonucleotides; D000099162:Endothelial PAS Domain-Containing Protein 1; C533794:EZN 2968; C497442:HIF1A protein, human
Alcoholic liver disease; Fatty liver; HIF1α; HIF2α; Hepatocellular carcinoma; Ischemia-reperfusion liver injury; Viral hepatitis