Hypoxia inducible factors in liver disease and hepatocellular carcinoma: current understanding and future directions

J Hepatol. 2014 Dec;61(6):1397-406. doi: 10.1016/j.jhep.2014.08.025. Epub 2014 Aug 23.

Abstract

Hypoxia inducible transcription factors (HIFs) activate diverse pathways that regulate cellular metabolism, angiogenesis, proliferation, and migration, enabling a cell to respond to a low oxygen or hypoxic environment. HIFs are regulated by oxygen-dependent and independent signals including: mitochondrial dysfunction, reactive oxygen species, endoplasmic reticular stress, and viral infection. HIFs have been reported to play a role in the pathogenesis of liver disease of diverse aetiologies. This review explores the impact of HIFs on hepatocellular biology and inflammatory responses, highlighting the therapeutic potential of targeting HIFs for an array of liver pathologies.

Keywords: HIF; Hypoxia; Inflammation; Liver; Viral hepatitis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / physiopathology*
  • Disease Models, Animal
  • Hepatovirus / physiology
  • Humans
  • Hypoxia-Inducible Factor 1 / physiology*
  • Liver / metabolism
  • Liver / virology
  • Liver Diseases / etiology
  • Liver Diseases / physiopathology*
  • Liver Neoplasms / etiology
  • Liver Neoplasms / physiopathology*
  • Mice
  • Oxygen / metabolism
  • Virus Diseases / physiopathology

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Hypoxia-Inducible Factor 1
  • endothelial PAS domain-containing protein 1
  • Oxygen