JCI table of contents: Nov. 21, 2007( A steady loss of kidney function ov...),Health

A steady loss of kidney function over a period of time is the characteristic symptom of chronic kidney disease (CKD). Kidney biopsy samples from individuals with CKD show the development of scar tissues (also known as fibrotic tissue). New data generated by Volker Haase and colleagues at the University of Pennsylvania, Philadelphia, has indicated a role for oxygen deficiency (hypoxia) in the formation of fibrotic tissue in the kidney.

In the study, elimination of the protein HIF-1-alpha (a key mediator of cellular responses to low oxygen) in kidney cells in mice inhibited the development of fibrotic tissue in a mouse model of kidney fibrosis. In vitro analysis indicated that HIF-1-alpha enhanced a process known as epithelial-to-mesenchymal transition (EMT), a key mechanism underlying the formation of fibrotic tissue, in mouse kidney cells in vitro. The clinical significance of these observations was highlighted by the demonstration that increased expression of HIF-1-alpha in the kidney was associated with tissue fibrosis in individuals with CDK. These data led the authors to suggest that therapies aiming to maintain adequate oxygen levels in the kidney might halt the progression of kidney fibrosis.

TITLE: Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition

AUTHOR CONTACT:

Volker H. Haase
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Phone: (215) 573-1846; Fax: (215) 746-5831; E-mail: vhaase@mail.med.upenn.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=30487

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Permanent kidney failure due to any cause is almost always accompanied by significant scarring, a disease state termed renal fibrosis. Protein a
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