Salvianolic acid B improves DEN/CCl4/C2H5OH-induced renal fibrosis by regulating YAP/TAZ and pSmad3C/pSmad3L

• Salvianolic acid B ameliorates DEN/CCl 4 /C 2 H 5 OH-induced renal fibrosis. • Salvianolic acid B downregulates YAP/TAZ levels and promotes their phosphorylation in renal fibrosis. • Salvianolic acid B upregulates pSmad3C level but downregulates pSmad3L level in renal fibrosis. • pSmad3L expression is significantly elevated due to the induction of MST1/2 inhibitor XMU-MP-1. Salvianolic acid B (Sal B) is a natural compound extracted from the root of Salvia miltiorrhiza , which has multiple biological activities. Targeting Hippo pathway transcriptional coactivators YAP/TAZ combined with Smad3 is an effective strategy against renal fibrosis. However, whether Sal B improves DEN/CCl 4 /C 2 H 5 OH-induced renal fibrosis and regulates YAP/TAZ and Smad3 phospho-isoform, pSmad3C/pSmad3L is unknown. Presently, we used DEN/CCl 4 /C 2 H 5 OH to induce renal fibrosis in mice and TGF-β1 or MST1/2 inhibitor XMU-MP-1 to induce HK-2 cells to investigate the activity and molecular mechanisms of Sal B. The results demonstrated that Sal B ameliorated DEN/CCl 4 /C 2 H 5 OH-induced renal fibrosis, including reducing renal tissue injury, improving renal function, and decreasing collagen synthesis. Furthermore, Sal B downregulated YAP/TAZ and promoted their phosphorylation in vivo and in vitro. Moreover, Sal B upregulated pSmad3C but downregulated pSmad3L in vivo and in vitro . Collectively, this study revealed that Sal B may improve DEN/CCl 4 /C 2 H 5 OH-induced renal fibrosis by regulating YAP/TAZ and pSmad3C/pSmad3L.