Hypoxia and hypoxia-inducible factor in renal disease

Masaomi Nangaku, Reiko Inagi, Toshio Miyata, Toshiro Fujita

Research output: Contribution to journalShort surveypeer-review

64 Citations (Scopus)

Abstract

Tissue hypoxia occurs when local metabolism is disturbed by an imbalance between oxygen supply and consumption. In patients with chronic kidney disease, chronic hypoxia in the kidneys is the end result of multiple processes and mechanisms. Once established, however, accumulating evidence points to this chronic hypoxia as the central player and final common pathway to end-stage renal disease. The cellular response to hypoxia is centered on hypoxia-inducible factor, HIF. This factor is composed of two subunits, an oxygen-sensitive HIF-α subunit and a constitutively expressed HIF-β subunit. Intracellular accumulation of HIF induces the coordinated expression of a number of adaptive genes against hypoxic insult.Three isoforms of HIF-α subunits have been identified, HIF-1α, HIF-2α, and HIF-3α, of which HIF-2α is involved in the regulation of erythropoietin as well as oxidative stress. HIF is regulated by prolyl hydroxylation and asparaginyl hydroxylation of the HIF-α subunit at the protein level. Because HIF is activated only to suboptimal levels in various pathogenic states, therapeutic activation holds promise as a novel and effective approach to the future care of end-stage renal disease.

Original languageEnglish
Pages (from-to)e1-e7
JournalNephron - Experimental Nephrology
Volume110
Issue number1
DOIs
Publication statusPublished - 2008 Sep

Keywords

  • Chronic kidney disease
  • Ischemia
  • Oxygen

ASJC Scopus subject areas

  • Physiology
  • Genetics
  • Nephrology

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