AUTHOR=Zou Junju , Zhou Xiaotao , Chen Xian , Ma Yuerong , Yu Rong 

TITLE=Shenkang Injection for Treating Renal Fibrosis-Metabonomics and Regulation of E3 Ubiquitin Ligase Smurfs on TGF-β/Smads Signal Transduction

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.849832

DOI=10.3389/fphar.2022.849832

ISSN=1663-9812

ABSTRACT=At present, TGF-β is the most critical fibrogenic factor known. Smad ubiquitin ligase Smurfs plays an important role in the regulation of TGF-β/Smads signaling pathway, and this pathway is closely related to the changes of metabolites in renal fibrosis. Previous studies have shown that Shenkang injection can prevent and treat chronic kidney disease through multiple channels of action. However, the specific relationship between Shenkang injection in the treatment of chronic kidney disease and the regulation of TGF-β/Smads signaling pathway remains unclear. Here, we evaluated the pharmacological effects of Shenkang injection on ubiquitination and metabolic changes of TGF-β/Smads signaling pathway in UUO mice using pathology-related indicators, immunoprecipitation, subcellular co-location, and metabonomics analysis. Our study showed that Shenkang injection could promote the nuclear translocation of Smurf1 and Smurf2 to TGF-β membrane receptors TβR-I and Smad2, and ubiquitinated degradation of them. Furthermore, the formation of TβR-I/TβR-II, TβR-I/Smad2, and TβR-I/Smad3 complexes was inhibited to negatively regulate the TGF-β/Smad signaling pathway induced renal tubular epithelial transdifferentiation (EMT). In addition, Shenkang injection can improve amino acid metabolism, purine metabolism, fatty acid metabolism disorder.