Wen-pi-tang-Hab-Wu-ling-san, an oriental herbal prescription, attenuates epithelial-mesenchymal transdifferentiation stimulated by TGF-beta1 in kidney cells

Abstract

Wen-pi-tang-Hab-Wu-ling-san (WHW), an oriental herbal prescription, is currently used in oriental clinics for the treatment of chronic renal failure (CRF). While its effectiveness has been supported by a series of modern studies, the underlying mechanism remains poorly understood. CRF progression involves tubulointerstitial fibrosis where transforming growth factor-beta1 (TGF-beta1) plays a critical role by inducing epithelial-mesenchymal transdifferentiation (EMT). This study examined whether WHW extract attenuated the TGF-beta1-induced EMT in Madin-Darby canine kidney cells. When the cells were stimulated by TGF-beta1 (2.5 ng/mL), they exhibited an elongated, spindle-shaped appearance but this morphological change was significantly suppressed by WHW extract (1 mg/mL). The WHW extract did not show notable cytotoxicity and even mitigated the cytotoxic effects of TGF-beta1. It inhibited the expression of alpha-smooth muscle actin (alpha-SMA), a marker of EMT, but not the secretion of matrix metalloproteinases stimulated by TGF-beta1. The WHW extract also inhibited the phosphorylation of Smad2 that mediates TGF-beta1 signaling leading to alpha-SMA expression. The present study suggests that WHW extract may provide renal protective effects through modulation of the TGF-beta1/Smad2/alpha-SMA pathway involved in fibrosis.