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Hypoxia-inducible factor signaling in the development of tissue fibrosis

Debra F. Higgins, Kuniko Kimura, Masayuki Iwano and Volker H. Haase

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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.

Authors

Debra F. Higgins

University of Pennsylvania School of Medicine; Philadelphia, PA

Kuniko Kimura

Nara Medical University; Kashihara, Nara, Japan

Masayuki Iwano

Nara Medical University; Kashihara, Nara, Japan

Volker H. Haase

University of Pennsylvania School of Medicine; Philadelphia, PA

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.