Increased AQP2 and AQP3 expression in renal cortex in COX‐2 deficient mice

Abstract

Previously we demonstrated that COX‐2 activity contributes to downregulation of aquaporin‐2 (AQP2) in rats subjected to 24h of bilateral ureteral obstruction (BUO). In this study we hypothesized that COX‐2 exerts tonic suppression of renal AQPs. We investigated the expression of AQPs and cyclooxygenase‐1 (COX‐1) in cortex (COR) and inner medulla (IM) tissue from COX‐2−/− mice. Kidneys from 4 week old COX‐2−/− (C57Bl6, 1. generation) mice and wild type (WT) littermates were prepared for semiquantitative immunoblotting. A subset of mice was perfusion fixed for immunohistochemistry (IHC). Plasma creatinine, osmolality and urea levels were increased in the COX‐2−/− mice compared to the WT. COX‐2 protein was not detectable in COX‐2−/− kidneys. COX‐1 abundance was increased in both COR and IM in COX‐2 KO mice compared to the WT. This was confirmed by IHC showing labeling of collecting ducts. AQP1 expression was unchanged in COR. AQP2 protein level was increased in COR of COX‐2−/− compared to WT but was not different in IM. The expression of AQP3 was increased in COR of COX‐2−/− mice and IHC showed intense labeling of the basolateral membranes of the cortical collecting ducts in the KO mice.The data indicate that COX‐2 is involved in regulation of the expression of AQP2 and AQP3. Further studies are required but our preliminary results indicate that COX‐2 may contribute to segmental regulation of water reabsorption.