Renal tubular arginase-2 participates in the formation of the corticomedullary urea gradient and attenuates kidney damage in ischemia-reperfusion injury in mice.

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Serval ID
serval:BIB_6D9085D98EB1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Renal tubular arginase-2 participates in the formation of the corticomedullary urea gradient and attenuates kidney damage in ischemia-reperfusion injury in mice.
Journal
Acta physiologica
Author(s)
Ansermet C., Centeno G., Lagarrigue S., Nikolaeva S., Yoshihara H.A., Pradervand S., Barras J.L., Dattner N., Rotman S., Amati F., Firsov D.
ISSN
1748-1716 (Electronic)
ISSN-L
1748-1708
Publication state
Published
Issued date
07/2020
Peer-reviewed
Oui
Volume
229
Number
3
Pages
e13457
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Arginase 2 (ARG2) is a mitochondrial enzyme that catalyses hydrolysis of l-arginine into urea and l-ornithine. In the kidney, ARG2 is localized to the S3 segment of the proximal tubule. It has been shown that expression and activity of this enzyme are upregulated in a variety of renal pathologies, including ischemia-reperfusion (IR) injury. However, the (patho)physiological role of ARG2 in the renal tubule remains largely unknown.
We addressed this question in mice with conditional knockout of Arg2 in renal tubular cells (Arg2 <sup>lox/lox</sup> /Pax8-rtTA/LC1 or, cKO mice).
We demonstrate that cKO mice exhibit impaired urea concentration and osmolality gradients along the corticomedullary axis. In a model of unilateral ischemia-reperfusion injury (UIRI) with an intact contralateral kidney, ischemia followed by 24 hours of reperfusion resulted in significantly more pronounced histological damage in ischemic kidneys from cKO mice compared to control and sham-operated mice. In parallel, UIRI-subjected cKO mice exhibited a broad range of renal functional abnormalities, including albuminuria and aminoaciduria. Fourteen days after UIRI, the cKO mice exhibited complex phenotype characterized by significantly lower body weight, increased plasma levels of early predictive markers of kidney disease progression (asymmetric dimethylarginine and symmetric dimethylarginine), impaired mitochondrial function in the ischemic kidney but no difference in kidney fibrosis as compared to control mice.
Collectively, these results establish the role of ARG2 in the formation of corticomedullary urea and osmolality gradients and suggest that this enzyme attenuates kidney damage in ischemia-reperfusion injury.
Keywords
arginase-2, arginine, kidney, kidney injury, proximal tubule, urea
Pubmed
Web of science
Funding(s)
Swiss National Science Foundation / Projects / 320030_170062
Create date
20/02/2020 16:27
Last modification date
28/12/2020 8:09
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