Vaccarin suppresses renal fibrosis in diabetic nephropathy through inhibiting EGFR signaling pathway

Abstract

Diabetic nephropathy (DN), one of the common chronic complications of diabetes, is the leading cause of end-stage renal disease. Vaccarin, a highly active Chinese medicinal monomer isolated from vaccariae semen, confers protective effects against type 2 diabetes mellitus (T2DM). However, the effects of vaccarin on kidney injury in diabetic nephropathy remain unknown. Our study showed that vaccarin ameliorated renal dysfunction and histological damage in diabetic kidneys through inhibiting renal fibrosis, overproduction of inflammation cytokine and reactive oxygen species (ROS). Additionally, vaccarin treatment significantly suppressed the process of epithelial-to-mesenchymal transition (EMT) in high glucose (HG)-induced HK-2 cells. In the mechanism, the network pharmacology analysis and molecular docking revealed that epidermal growth factor receptor (EGFR) may be the potential target of vaccarin. Furthermore, the phosphorylation of EGFR as well as EKR1/2 were abrogated by vaccarin in diabetic nephropathy and HG-treated HK-2 cells. In conclusion, our results reveal that vaccarin attenuates diabetic renal fibrosis via inactivation of EGFR signaling. Vaccarin might be a potential drug to alleviate diabetic nephropathy.