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.
Division for Health Service Promotion, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Tetsuhiro
T
Tanaka
Masaomi
M
Nangaku
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