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

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 mCCD 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.

The enzyme L‐arginase type 2 in proximal tubular epithelium links urea accumulation and protection against ischemic insults in kidney

“…A 12h water deprivation challenge did not unravel any difference in urine volume and osmolality and no significant change in medullary aquaporin 2 protein abundance 1 . This observation was in sharp contrast to published observations by Huang et al 7 who showed enhanced urine concentration in absence of ARG2. Why this apparent difference since both studies used 12 hours of water deprivation in adult C57BL6 mice?…”

“…Why this apparent difference since both studies used 12 hours of water deprivation in adult C57BL6 mice? Whereas Ansermet et al 1 used male mice and inducible disruption of ARG2, Huang et al 7 did not report mice sex and used germline global deletion of ARG2. At baseline, kidney medulla tissue urea was decreased by ARG2 deletion 1 .…”

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

“…These hypotheses and results, however, have not been supported in studies using Arg2 ‐null mouse model or arginase inhibitors. For instance, Huang et al have recently demonstrated that Arg2 ‐null mice exhibit greater urine concentration capacity under water deprivation . Morris et al have shown that diabetic renal injury was significantly attenuated in ARG2‐null mice or wild‐type mice treated with an arginase inhibitor .…”

Alismatis Rhizoma Triterpenes Regulate Metabolism of Renal Cells by AQP-2

“…AQP-2 improves water permeability when transported to the apical membrane of the cell. The evidence showed that it can promote the reabsorption of water and the concentration of urine, reducing plasma osmotic pressure finally (Huang et al 2018).…”