Wen-pi-tang-Hab-Wu-ling-san, an oriental herbal prescription, attenuates epithelialmesenchymal transdifferentiation stimulated by TGF-β1 in kidney cells

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-β1 (TGF-β1) plays a critical role by inducing epithelial-mesenchymal transdifferentiation (EMT). This study examined whether WHW extract attenuated the TGF-β1-induced EMT in Madin-Darby canine kidney cells. When the cells were stimulated by TGF-β1 (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-β1. It inhibited the expression of α-smooth muscle actin (α-SMA), a marker of EMT, but not the secretion of matrix metalloproteinases stimulated by TGF-β1. The WHW extract also inhibited the phosphorylation of Smad2 that mediates TGF-β1 signaling-leading to α-SMA expression. The present study suggests that WHW extract may provide renal protective effects through modulation of the TGF-β1/Smad2/α-SMA pathway involved in fibrosis.