Genetic targeting of arginase-ii in mouse prevents renal oxidative stress and inflammation in diet-induced obesity

Huang, Ji; Rajapakse, Angana; Xiong, Yuyan; Montani, Jean-Pierre; Verrey, François; Ming, Xiu-Fen; Yang, Zhihong

doi:10.3389/fphys.2016.00560

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Journal article

Genetic targeting of arginase-ii in mouse prevents renal oxidative stress and inflammation in diet-induced obesity

Huang, Ji Cardiovascular and Aging Research, Division of Physiology, Department of Medicine, University of Fribourg, Switzerland - Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis “Kidney.CH”, Zurich, Switzerland
Rajapakse, Angana Cardiovascular and Aging Research, Division of Physiology, Department of Medicine, University of Fribourg, Switzerland
Xiong, Yuyan Cardiovascular and Aging Research, Division of Physiology, Department of Medicine, University of Fribourg, Switzerland
Montani, Jean-Pierre Cardiovascular and Aging Research, Division of Physiology, Department of Medicine, University of Fribourg, Switzerland - Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis “Kidney.CH”, Zurich, Switzerland
Verrey, François Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis “Kidney.CH”, Zurich, Switzerland - Institute of Physiology, University of Zurich, Switzerland
Ming, Xiu-Fen Cardiovascular and Aging Research, Division of Physiology, Department of Medicine, University of Fribourg, Switzerland - Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis “Kidney.CH”, Zurich, Switzerland
Yang, Zhihong Cardiovascular and Aging Research, Division of Physiology, Department of Medicine, University of Fribourg, Switzerland - Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis “Kidney.CH”, Zurich, Switzerland

2016

Published in:

Frontiers in Physiology. - 2016, vol. 7, p. 560

English Obesity is associated with development and progression of chronic kidney disease (CKD). Recent evidence demonstrates that enhanced levels of the L- arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I) and arginase- II (Arg-II) in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS), leading to increased superoxide radical anion and decreased NO production thereby endothelial dysfunction. Arg-II but not Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is uncertain and controversial. We aimed to investigate the role of Arg-II in renal damage associated with diet-induced obesity mouse model. Wild type (WT) C57BL/6 mice and mice deficient in Arg-II gene (Arg-II^−/−) were fed with either a normal chow (NC) or a high-fat-diet (HFD) for 14 weeks (starting at the age of 7 weeks) to induce obesity. In WT mice, HFD feeding caused frequent renal lipid accumulation, enhancement of renal reactive oxygen species (ROS) levels which could be attenuated by a NOS inhibitor, suggesting uncoupling of NOS in kidney. HFD feeding also significantly augmented renal Arg-II expression and activity. All the alterations in the kidney under HFD feeding were reduced in Arg-II^−/− mice. Moreover, mesangial expansion as analyzed by Periodic Acid Schiff (PAS) staining and renal expression of vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HFD-fed WT mouse assessed by immunoblotting were reduced in the HFD-fed Arg- II^−/− mice, although there was no significant difference in body weight and renal weight/body weight ratio between the WT and Arg-II^−/− mice. Thus, Arg-II expression/activity is enhanced in kidney of diet-induced obesity mice. Genetic targeting of Arg-II prevents renal damage associated with obesity, suggesting an important role of Arg-II in obesity-associated renal disease development.

Faculty

Faculté des sciences et de médecine

Department

Département de Médecine

Language