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Physiology (Bethesda). 2009 Apr;24:97-106. doi: 10.1152/physiol.00045.2008.

Regulation of oxygen homeostasis by hypoxia-inducible factor 1.

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Vascular Program, Institute for Cell Engineering, McKusick-Nathans Institute of Genetic Medicine, Baltimore, Maryland, USA.


Metazoan organisms are dependent on a continuous supply of O(2) for survival. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates oxygen homeostasis and plays key roles in development, physiology, and disease. HIF-1 activity is induced in response to continuous hypoxia, intermittent hypoxia, growth factor stimulation, and Ca(2+) signaling. HIF-1 mediates adaptive responses to hypoxia, including erythropoiesis, angiogenesis, and metabolic reprogramming. In each case, HIF-1 regulates the expression of multiple genes encoding key components of the response pathway. HIF-1 also mediates maladaptive responses to chronic continuous and intermittent hypoxia, which underlie the development of pulmonary and systemic hypertension, respectively.

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