Ecliptasaponin A attenuates renal fibrosis by regulating the extracellular matrix of renal tubular cells

Renal fibrosis is the most common manifestation of end-stage renal disease (ESRD), including diabetic kidney disease (DKD), but there is no effective treatment in renal fibrosis. Natural products are a rich source of clinical drug research and have been used in the clinical research of various diseases. In this study, we searched for traditional Chinese medicine monomers that attenuate fibrosis and assessed their effect on the fibrosis marker connective tissue growth factor (CTGF) in cells which we found ecliptasaponin A. Subsequently, we evaluated the effect of ecliptasaponin A on renal fibrosis in the classic renal fibrosis unilateral ureteral obstruction (UUO) mouse model and found that ecliptasaponin A could reduce the renal collagen fiber deposition and renal extracellular matrix (ECM) protein expression in UUO mice. In vitro, ecliptasaponin A can inhibit ECM protein expression in human kidney-2 (HK-2) cells induced by transforming growth factor-beta1 (TGF beta 1). To further clarify the mechanism of ecliptasaponin A in attenuating renal fibrosis, we performed transcriptome sequencing of HK-2 cells treated with TGF beta 1 and ecliptasaponin A. The functions and pathways were mainly enriched in the extracellular matrix and TGF beta signalling pathway. Matrix metalloproteinase 10 (MMP10) and matrix metalloproteinase 13 (MMP13) are the main differentially expressed genes in extracellular matrix regulation. Then, we measured MMP10 and MMP13 in the cells and found that ecliptasaponin A had a significant inhibitory effect on MMP13 expression but not on MMP10 expression. Furthermore, we overexpressed MMP13 in HK-2 cells treated with TGF beta 1 and found that MMP13 promoted HK-2 cell injury. Our findings suggest that ecliptasaponin A can attenuate renal fibrosis, which may provide a new method for treating renal fibrosis clinically.

Automated summary

This study found that ecliptasaponin A can attenuate renal fibrosis and inhibit the expression of key ECM proteins in the fibrosis process. The study also revealed the regulatory role of ecliptasaponin A in the TGF-beta signaling pathway and the importance of MMP13 in extracellular matrix regulation.