Hypoxia-inducible factor signaling in the development of tissue fibrosis

Cell Cycle. 2008 May 1;7(9):1128-32. doi: 10.4161/cc.7.9.5804. Epub 2008 Feb 11.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Epithelial Cells / metabolism
  • Extracellular Matrix / metabolism
  • Fibrosis / genetics
  • Fibrosis / metabolism*
  • Fibrosis / physiopathology
  • Humans
  • Hypoxia / metabolism*
  • Hypoxia / physiopathology
  • Hypoxia-Inducible Factor 1 / genetics
  • Hypoxia-Inducible Factor 1 / metabolism*
  • Mesoderm / metabolism
  • Nephritis, Interstitial / metabolism*
  • Nephritis, Interstitial / physiopathology
  • Regional Blood Flow / physiology
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Hypoxia-Inducible Factor 1
  • Transforming Growth Factor beta1