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Arginase‐2 protects the kidney against ischemia‐reperfusion injury
Author(s) -
Ansermet Camille,
Centeno Gabriel,
Rotman Samuel,
Barras JeanLuc,
Dattner Nicolas,
Firsov Dmitri
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.849.3
Subject(s) - arginase , acute kidney injury , downregulation and upregulation , endocrinology , medicine , kidney , renal ischemia , albuminuria , ischemia , reperfusion injury , chemistry , arginine , biochemistry , amino acid , gene
Arginase‐2 (Arg2) is an enzyme converting the L‐arginine in urea and L‐ornithine. As it is expressed in extra‐hepatic tissues lacking a complete urea cycle, it may play a role in polyamines production, nitric oxide regulation or energy supply. Arg2 expression has been shown to be induced by hypoxia, in vitro and in vivo , and interestingly, its upregulation has been observed in certain animals naturally exposed to low oxygen concentration. Moreover, Arg2 overexpression has been associated with many pathological conditions, as diabetes, atherosclerosis, cardiac and renal ischemia reperfusion and cirrhosis, or after toxic compounds exposure (cadmium, cisplatin). Although Arg2 inhibition seems to improve the disease severity, the role of this upregulation remains unknown. We hypothesized that Arg2 upregulation in renal cells following an ischemic event helps the cells to overcome the occlusion‐induced stress. To address this question, we used the Pax8‐rtTA‐driven Cre expression system, allowing a conditional inactivation of Arg2 in mouse renal tubule. The conditional Arg2 knockout mice (cKO) subjected to 25‐minute renal ischemia followed by 24‐hour reperfusion show a more severe acute kidney injury (AKI) compared to Control mice and develop a transient renal Fanconi syndrome characterized by polyuria, albuminuria, aminoaciduria, hypercalcuria, hypermagnesuria and phosphaturia. When the reperfusion time increases to 2 weeks, urinary parameters normalize in both groups, but cKO mice show an increase in renal insufficiency markers compared to Control mice, with higher plasma levels of asymmetric (ADMA) and symmetric (SDMA) dimethylarginine. Taken together, these results support a relevant role for Arg2 in renal ischemia recovery. Support or Funding Information Swiss National Science Foundation Research grants 31003A‐149440 (to D.F.) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .