Saikosaponin D Inhibits Peritoneal Fibrosis in Rats With Renal Failure by Regulation of TGFβ1/ BMP7 / Gremlin1/ Smad Pathway

Abstract

Peritoneal dialysis (PD) can improve the quality of life of patients with kidney disease and prolong survival. However, peritoneal fibrosis can often occur and lead to PD withdrawal. Therefore, it is imperative to better understand how to inhibit and slow down progression of peritoneal fibrosis. This study aimed to investigate the regulatory effect of Saikosaponin d (SSD), a monomer extracted from the plant Bupleurum, on peritoneal fibrosis and the contribution of TGFβ1/BMP7/Gremlin1 pathway cross-talk in this process. To this aim, we used a model 5/6 nephrectomy and peritoneal fibrosis in rats. Rats were divided into four groups, namely a control group (saline administration); a model group (dialysate administration; group M); a SSD group (dialysate and SSD administration); and a positive drug group (dialysate and Benazepril Hydrochloride administration; group M + A). Histological analysis indicated that peritoneal fibrosis occurred in all groups. WB, ELISA, and PCR essays suggested that TGFβ1 and Gremlin1 levels in group M were significantly higher than those in group C, whereas BMP7 expression was significantly lower. TGFβ1, Gremlin1 and BMP7 levels were significantly lower in the group where SSD was administered than in the other groups. The expression of BMP7 in SSD group was significantly increased. In addition, levels of Smad1/5/8 as assessed by PCR, and levels of p-Smad1/5/8 expression as assessed by WB were also significantly higher in the SSD group than in the M group. Expression of vimentin and α-SMA, two important markers of fibrosis, was also significantly decreased. Our study suggests a role for the TGFβ1/BMP7/Gremlin1/Smad pathway in peritoneal fibrosis with potential therapeutic implications. Finally, our results also suggest that the monomer SSD may be able to reverse peritoneal fibrosis via regulation of the TGFβ1/BMP7/Gremlin1/Smad pathway.

Brahma-related gene 1 acts as a profibrotic mediator and targeting it by micheliolide ameliorates peritoneal fibrosis

“…However, despite these findings, challenges still exist. MCL can simultaneously regulate multiple targets [ 29 , 48 , 52 ] and might be involved in complicated feedback mechanisms, therefore, more experimental PD animal models, including chlorhexidine gluconate-induced peritoneal fibrosis model [ 53 , 54 ] and rat model with chronic renal failure resulting from 5/6 nephrectomy [ 55 ] are needed to corroborate its efficacy in peritoneal fibrosis. Moreover, safety and effectiveness clinical trials should be conducted to assess the use of MCL in this context.…”

Astragaloside IV Alleviates Intestinal Barrier Dysfunction via the AKT-GSK3β-β-Catenin Pathway in Peritoneal Dialysis

“…End-stage renal disease (ESRD) is the final result of the progressive development of chronic kidney disease (CKD), and its incidence has increased in recent years ( Yamagata et al, 2015 ; McCullough et al, 2019 ; Ruiqi et al, 2021 ). Peritoneal dialysis (PD) is a renal replacement therapy for patients with ESRD ( Mehrotra et al, 2016 ; Li et al, 2017 ), allowing patients to undergo dialysis at home, which is cost-effective and highly tolerable.…”