Salvianolic Acid C Inhibits the Epithelial-Mesenchymal Transition and Ameliorates Renal Tubulointerstitial Fibrosis
Ming Wu, Junyan Lin, Di Huang, Chaoyang Ye, Dong‐Ping Chen
Abstract
BACKGROUND: that can protect against renal diseases. The aims of this work were to explore the effect of SAC on kidney tubulointerstitial fibrosis and study the associated mechanism. METHODS: Models for unilateral ureteral obstruction (UUO) and aristolochic acid I (AAI) were established in mice to study renal tubulointerstitial fibrosis. Rat kidney fibroblasts (NRK-49F) and human kidney epithelial cells (HK2) were used as cellular models to evaluate the effects of SAC on kidney fibrosis. RESULTS: Treatment with SAC for two weeks reduced the level of renal tubulointerstitial fibrosis in UUO- and AAI-induced fibrotic kidneys, as demonstrated by Masson's staining and Western blot. SAC inhibited extracellular matrix protein expression in NRK-49F cells and TGF-β-stimulated HK2 cells in dose-dependent fashion. Moreover, SAC inhibited the expression of epithelial-mesenchymal transition (EMT) factors in animal and cellular models of kidney fibrosis, as well as the EMT-related transcription factor snail. Furthermore, SAC inhibited the fibrosis-related signaling pathway Smad3 in the fibrotic kidneys of two mouse models and in renal cells. CONCLUSIONS: We conclude that SAC inhibits EMT and ameliorates tubulointerstitial fibrosis through involvement of the signaling pathway for transforming growth factor-β (TGF-β)/Smad.