The role of hypoxia, increased oxygen consumption, and hypoxia-inducible factor-1 alpha in progression of chronic kidney disease.
OBJECTIVE
Tubulointerstitial hypoxia in the kidney has been considered a hallmark of injury and mediator of disease progression. This review focuses on hypoxia-inducible factor (HIF)-1, a master transcription factor in cellular adaptation to hypoxia.


RESULTS
HIF-1alpha is expressed in the hypoxic tubular epithelium as well in as the papillary interstitium and glomerular epithelial cells. Although HIF-1 plays a protective role in a number of acute kidney injury models when overexpressed, its activation in chronic kidney disease results in multiple phenotypic changes, depending on the pathological context.


CONCLUSIONS
Hypoxia, especially HIF-1, is a critical mediator in the pathogenesis of chronic kidney disease. Underlying molecular mechanisms, together with responsible HIF target genes, are currently under investigation.
Tanaka
Tetsuhiro
T
Division for Health Service Promotion, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Nangaku
Masaomi
M
D000818:Animals; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D007668:Kidney / Q000098:blood supply / Q000293:injuries / Q000503:physiopathology; D010101:Oxygen Consumption; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D017434:Protein Structure, Tertiary; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011393:Procollagen-Proline Dioxygenase