Hypoxia-inducible factor signaling in the development of tissue fibrosis.
Capillary rarefaction is a hallmark of fibrotic diseases and results in reduced blood perfusion and oxygen delivery. In the kidney, tubulointerstitial fibrosis, which leads to the destruction of renal tissue and the irreversible loss of kidney function, is associated with hypoxia and the activation of Hypoxia-Inducible-Factor (HIF) signaling. HIF-1 and HIF-2 are basic-helix-loop-helix transcription factors that allow cells to survive in a low oxygen environment by regulating energy metabolism, vascular remodeling, erythropoiesis, cellular proliferation and apoptosis. Recent studies suggest that HIF activation promotes epithelial to mesenchymal transition (EMT) and renal fibrogenesis. These findings raise the possibility that the spectrum of HIF activated biological responses to hypoxic stress may differ under conditions of acute and chronic hypoxia. Here we discuss the role of HIF signaling in the pathogenesis and progression of chronic kidney disease.
Higgins
Debra F
DF
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA.
Kimura
Kuniko
K
Iwano
Masayuki
M
Haase
Volker H
VH
D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism; D009395:Nephritis, Interstitial / Q000378:metabolism* / Q000503:physiopathology; D012039:Regional Blood Flow / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D051793:Hypoxia-Inducible Factor 1; D053773:Transforming Growth Factor beta1