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Arginase-II negatively regulates renal aquaporin-2 and water reabsorption

Huang, Ji
Montani, Jean-Pierre
Verrey, François
Ming, Xiu-Fen
Yang, Zhihong
Published in FASEB Journal. 2018, vol. 32, no. 10, p. 5520-5531
Abstract Type-II l-arginine:ureahydrolase, arginase-II (Arg-II), is abundantly expressed in the kidney. The physiologic role played by Arg-II in the kidney remains unknown. Herein, we report that in mice that are deficient in Arg-II (Arg-II-/-), total and membrane-associated aquaporin-2 (AQP2) protein levels were significantly higher compared with wild-type (WT) controls. Water deprivation enhanced Arg-II expression, AQP2 levels, and membrane association in collecting ducts. Effects of water deprivation on AQP2 were stronger in Arg-II-/- mice than in WT mice. Accordingly, a decrease in urine volume and an increase in urine osmolality under water deprivation were more pronounced in Arg-II-/- mice than in WT mice, which correlated with a weaker increase in plasma osmolality in Arg-II-/- mice. There was no difference in vasopressin release under water deprivation conditions between either genotype of mice. Although total AQP2 and phosphorylated AQP2-S256 levels (mediated by PKA) in kidneys under water deprivation conditions were significantly higher in Arg-II-/- mice compared with WT animals, there is no difference in the ratio of AQP2-S256:AQP2. In cultured mouse collecting duct principal mCCDcl1 cells, expression of both Arg-II and AQP2 were enhanced by the vasopressin type 2 receptor agonist, desamino- d-arginine vasopressin (dDAVP). Silencing Arg-II enhanced the expression and membrane association of AQP2 by dDAVP without influencing cAMP levels. In conclusion, in vivo and in vitro experiments demonstrate that Arg-II negatively regulates AQP2 and the urine-concentrating capability in kidneys via a mechanism that is not associated with the modulation of the cAMP pathway.-Huang, J., Montani, J.-P., Verrey, F., Feraille, E., Ming, X.-F., Yang, Z. Arginase-II negatively regulates renal aquaporin-2 and water reabsorption.
PMID: 29718707
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Research group Laboratoire de physiologie et pathophysiologie des cellules rénales (29)
Project NCCR Kidney.ch
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HUANG, Ji et al. Arginase-II negatively regulates renal aquaporin-2 and water reabsorption. In: FASEB Journal, 2018, vol. 32, n° 10, p. 5520-5531. doi: 10.1096/fj.201701209R https://archive-ouverte.unige.ch/unige:109580

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Deposited on : 2018-10-23

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