Oxygen-regulated transcription factors and their role in pulmonary disease.
The transcription factors nuclear factor interleukin-6 (NF-IL6), early growth response-1 (EGR-1) and hypoxia-inducible factor-1 (HIF-1) have important roles in the molecular pathophysiology of hypoxia-associated pulmonary disease. NF-IL6 controls the production of interleukin (IL)-6 in vascular endothelial cells, which may have anti-inflammatory activity by counteracting effects of IL-1 and IL-8. EGR-1 controls the production of tissue factor by macrophages, which triggers fibrin deposition in the pulmonary vasculature. HIF-1 activates the expression of the vasoconstrictor endothelin-1 in vascular endothelial cells. Angiotensin II induces HIF-1 expression and hypertrophy of pulmonary arterial smooth muscle cells. HIF-1 might therefore have multiple roles in the pathogenesis of pulmonary vascular remodeling.
Semenza
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Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. gsemenza@jhmi.edu
D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1; D008171:Lung Diseases / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D022782:CCAAT-Enhancer-Binding Protein-beta; D004268:DNA-Binding Proteins; D051793:Hypoxia-Inducible Factor 1; D009687:Nuclear Proteins; D014157:Transcription Factors; D010100:Oxygen