Effect of Oryeongsan on hypertonic stress‐induced water channel expression and apoptosis in renal collecting duct cells

Abstract

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. Oryeongsan (ORS, Wulingsan) has been reported to possess renal protective effects from renal diseases such as diabetes‐induced renal damage, nephrocalcinosis. This study was conducted to evaluate the inhibitory effect of ORS on hypertonic stress‐induced AQP2 expression and apoptosis in inner medullary collecting duct cell lines (IMCD‐3). Hypertonic stress (175 mM NaCl) increased AQP2 expression, ORS attenuated the hypertonicity‐induced increase in protein and mRNA levels in a concentration‐dependent manner. Pretreatment with ORS attenuated hypertonicity‐induced cell death. Hypertonicity increased serum‐ and glucocorticoid‐inducible protein kinase (Sgk1) phosphorylation, however, ORS attenuated the hypertonicity‐induced Sgk1 activation. Tonicity‐responsive enhancer binding protein (TonEBP) mRNA was also recovered by ORS under hypertonic stress. Hypertonicity increased cAMP levels and the changes were blocked by ORS. On the other hand, hypertonic stress‐induced Bax or caspase‐3 expression was decreased by ORS, resulting in anti‐apoptotic effect. These results provided evidence that the beneficial effect of ORS in water balance and apoptosis against in vitro hypertonic stress of renal collecting ducts.