ADAMTS16 and TRPV5: New targets of Zhenwu decoction on renal fibrosis investigated by chemomics and transcriptomics

Abstract

Renal fibrosis (RF) plays a crucial role in the transition from different forms of CKD to ESRD, recognized as the primary pathological change in chronic kidney disorders. Previous study demonstrated that Zhenwu decoction (ZWD) is efficacious in the treatment of RF whether initiated in the early or the late stage. To elucidate the molecular mechanisms of ZWD on RF treatment and to propose novel potential targets for therapeutic intervention in RF treatment, qualitative chemomics strategy was conducted to search the potential active compounds of ZWD by UPLC-Q-TOF/MS. And transcriptomic analysis and pathway enrichment was utilized to identify key regulatory genes and signaling involved in medicine and RF conditions. As a result, aconite alkaloids and paeoniflorin were identified as the principal pharmacodynamic constituents, while ADAMTS16 and TRPV5 emerged as novel targets of ZWD in the context of RF. Importantly, the robust expression of ADAMTS16 and TRPV5 in the kidney highlights their potential as therapeutic targets for RF.