salvianolic-acid-c and Fibrosis

Salvianolic acid C (SAC) is a natural compound derived from. 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.. 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.. We conclude that SAC inhibits EMT and ameliorates tubulointerstitial fibrosis through involvement of the signaling pathway for transforming growth factor-β (TGF-β)/Smad.

Topics: Animals; Epithelial-Mesenchymal Transition; Fibrosis; Humans; Kidney Diseases; Mice; Rats; Transforming Growth Factor beta; Transforming Growth Factor beta1; Ureteral Obstruction