Wen‐pi‐tang‐Hab‐Wu‐ling‐san, an oriental herbal prescription, attenuates epithelial‐mesenchymal transdifferentiation stimulated by TGF‐β1 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‐ β 1 (TGF‐ β 1) plays a critical role by inducing epithelial‐mesenchymal transdifferentiation (EMT). This study examined whether WHW extract attenuated the TGF‐ β 1‐induced EMT in Madin‐Darby canine kidney cells. When the cells were stimulated by TGF‐ β 1 (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‐ β 1. 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‐ β 1. The WHW extract also inhibited the phosphorylation of Smad2 that mediates TGF‐ β 1 signaling leading to α ‐SMA expression. The present study suggests that WHW extract may provide renal protective effects through modulation of the TGF‐ β 1/Smad2/ α ‐SMA pathway involved in fibrosis. Copyright © 2007 John Wiley & Sons, Ltd.