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A novel renal carbonic anhydrase type III plays a role in proximal tubule dysfunction

Item Type:Article
Title:A novel renal carbonic anhydrase type III plays a role in proximal tubule dysfunction
Creators Name:Gailly, P. and Jouret, F. and Martin, D. and Debaix, H. and Parreira, K.S. and Nishita, T. and Blanchard, A. and Antignac, C. and Willnow, T.E. and Courtoy, P.J. and Scheinman, S.J. and Christensen, E.I. and Devuyst, O.
Abstract:Dysfunction of the proximal tubule (PT) is associated with variable degrees of solute wasting and low-molecular-weight proteinuria. We measured metabolic consequences and adaptation mechanisms in a model of inherited PT disorders using PT cells of ClC-5-deficient (Clcn5Y/-) mice, a well-established model of Dent's disease. Compared to cells taken from control mice, those from the mutant mice had increased expression of markers of proliferation (Ki67, proliferative cell nuclear antigen (PCNA), and cyclin E) and oxidative scavengers (superoxide dismutase I and thioredoxin). Transcriptome and protein analyses showed fourfold induction of type III carbonic anhydrase in a kidney-specific manner in the knockout mice located in scattered PT cells. Kidney-specific carbonic anhydrase type III (CAIII) upregulation was confirmed in other mice lacking the multiligand receptor megalin and in a patient with Dent's disease due to an inactivating CLCN5 mutation. The type III enzyme was specifically detected in the urine of mice lacking ClC-5 or megalin, patients with Dent's disease, and in PT cell lines exposed to oxidative stress. Our study shows that lack of PT ClC-5 in mice and men is associated with CAIII induction, increased cell proliferation, and oxidative stress.
Keywords:Cell and Transport Physiology, Cell Survival, Genetic Renal Disease, Endocytosis, Oxidative Stress, Animals, Mice
Source:Kidney International
Publisher:Nature Publishing Group (U.S.A.)
Page Range:52-61
Date:1 July 2008
Official Publication:https://doi.org/10.1038/sj.ki.5002794
PubMed:View item in PubMed

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