Abstract: PO1293
H2S May Inhibit Peritoneal Dialysis-Related Fibrosis Through the Sulfhydrylation Regulation of PSMA7
Session Information
- Peritoneal Dialysis - 2
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 703 Dialysis: Peritoneal Dialysis
Authors
- Chen, Xujiao, Department of Nephrology, Second Affiliated hospital of Zhejiang University, Hangzhou, China
- Hu, Ying, Department of Nephrology, Second Affiliated hospital of Zhejiang University, Hangzhou, China
Background
Peritoneal dialysis (PD) is one of the first treatment methods for patients with end-stage renal disease, which has advantages on cardiovascular system protection, large toxin clearance and patients' life quality improvement. But statistics shows that the 5-year withdrawal rate of PD patients was around 50%, and ultrafiltration failure caused by peritoneal fibrosis is the main reason, and there is no effective clinical prevention and treatment. In our previous study, we found that the flora of PD patients was obviously maladjusted, and the production of H2S in the intestine was significantly reduced. Some evidences showed that H2S may alleviate PD-related fibrosis, suggesting that H2S may affect the fibrosis by regulating the level of sulfhydrylation, but the mechanism is not clear.
Methods
Rat peritoneal mesothelial cells were randomly assigned into different groups, 4.5% peritoneal dialysate group (PD group), PD+H2S supplement GYY4137 group and PD+H2S inhibitor PAG group. The expression of pyroptosis associated proteis, inflammatory factors and fibrosis related pathways in different groups were compared. The changes of protein sulfhydryl sulfhydrylation level were analyzed by HPLC/MS/ MS. The target protein and related pathway protein were up/down regulated by SiRNA and the downstream pathways expression were observed by PCR and Western blot.
Results
GYY4137 significantly reduced the expression of pyroptosis proteins (NLRP3, ccas-1, gsdmd-n), inflammatory factors (IL-6, IL-8, TNF - α) and fibrosis related proteins (p-smad3, Smad, TGF-β, VEGF) response to high glucose PD fluid. We found that the level of PSAM-7 sulfhydrylation in the PD group decreased significantly, but in GYY4137 group, the level of PSMA7 ulfhydrylation increased significantly. The expression of pyroptosis proteins, inflammatory factors and fibrosis related proteins were significantly increased after PSMA7 sulfhydrylation was interfered by mutant plasmids. The expression level of NLRP3 was up/down regulated by siRNA. The expression of downstream inflammatory factors and fibrosis-related proteins were significantly increased/decreased.
Conclusion
H2S has a protective effect on PD-related fibrosis through the PSMA7 sulfhydryl sulfhydrylation regulation, and further break the pathological changes of "pyroptosis- inflammation-fibrosis" axis and avoid the occurrence of inflammatory cascade reaction.