Abstract

A major physiological role of the kidney is to regulate body water and urine concentration. Aquaporin-2 (AQP2), a family of water channels, plays an important role in the urinary concentrating process and regulation of water balance in the kidney. The dried sclerotia of Poria cocos Wolf (WPC) is a well-known Oriental medicinal plant that grows around the roots of pine trees. WPC has been known to have a diuretic effect and used for the treatment of chronic diabetic and nephrosis. Experiments were performed in mouse inner medullary collecting duct (mIMCD-3) cell line. Hypertonic stress was applied with hypertonic (NaCl 175 mM) solution. We confirmed hypertonicity-induced increased in AQP2 expression. WPC (10 – 50 mg/ml) attenuated the hypertonicity-induced protein and mRNA levels of AQP2 in a concentration-dependent manner. It identified expression of SMIT to verify through the agency of transcription factor tonicity-responsive enhancer binding protein (TonEBP). Hypertonicity increased the levels of TonEBP and SMIT mRNA. WPC attenuated the hypertonicity-induced TonEBP and SMIT levels. Similaly, WPC attenuated the hypertonicity-induced phosphorylated-SGK, but not SGK. Furthermore, hypertonicity increased cAMP levels and the changes were blocked by WPC. Taken together, the present data suggest that WPC inhibits hypertonicity-induced AQP2 expression via SGK, TonEBP and cAMP signaling pathway.

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