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Acta Physiologica 2012; Volume 204, Supplement 689
91st Annual Meeting of The German Physiological Society
3/22/2012-3/25/2012
Dresden, Germany
THE NADPH OXIDASE NOX4 IS PROTECTIVE RATHER THAN DELETERIOUS FOR RENAL FUNCTION
Abstract number: P249
Babelova1 *A., Avaniadi1 D., Jung1 O., Schroder1 K., Brandes1 R.P.
1Goethe-Universitt, Institut fr Kardiovaskulre Physiologie, Frankfurt am Main, Germany
Nox4 is a hydrogen peroxide producing NADPH oixdase which is highly expressed in the kidney. Nox4 has been linked to epithelial cell injury and diabetic-induced cellular dysfunction in cell culture studies. With the aid of our global and inducible Nox4 knockout mice, we tested the relevance of the protein for murine kidney disease.
Acute deletion of Nox4 by a tamoxifen-driven induction of the cre-recombinase had no effect on streptozotocin-diabetes-induced albuminuria and accumulation of glomerular matrix proteins. This lack of effect was maintained in subgroups receiving co-application of angiotensin II. Interestingly, Nox4 expression was rather down-regulated than increased as suggested by others under these conditions. Similarly, in the mouse remnant kidney model, development of hypertension and albuminuria was similar between wildtype and global Nox4-/- mice. Finally, we induced renal fibrosis by unilateral ureter ligation. In this model of tubulointerstitial fibrosis, kidneys from NOX4-deficient mice were lighter and displayed enhanced accumulation of fibronectin compared to wild-type counterparts.
Our results indicate that NOX4 is not a main driver of progressive renal disease. It rather appears that under specific conditions Nox4 may even limit injury and disease progression. Thus, Nox4 could be protective rather than deleterious for renal function.
To cite this abstract, please use the following information:
Acta Physiologica 2012; Volume 204, Supplement 689 :P249