Abstract: SA-PO939
Inhibition of mPGES-1 Blocks High Glucose-Induced Mesothelial-to-Mesenchymal Transition of Peritoneal Mesothelial Cells
Session Information
- Dialysis: Peritoneal Dialysis - III
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 703 Dialysis: Peritoneal Dialysis
Author
- Luo, Qimei, Shunde Hospital of Southern Medical University, Foshan, China
Background
Peritoneal mesangial cells (PMC) undergoing mesothelial-to-mesenchymal transition (MMT) induced by chronic sterile inflammation promotes peritoneal fibrosis. Microsomal prostaglandin E2 synthase-1 (mPGES-1)-derived PGE2 plays an important role in inflammatory disease. Previous studies have shown that the secretion of PGE2 increased significantly in PMC under the circumstance of high glucose. This study aimed to investigate the role of mPGES-1 in phenotype transition of PMC.
Methods
The expression of mPGES-1 in human peritoneum tissue was evaluated by immunohistochemical. Human mesothelial cells were incubated with 138mmol/L glucose for various periods of time. After transfection of shRNA plasmid targeting mPGES-1, human mesothelial cells were incubated with 138mmol/L glucose and harvested for further analysis.
Results
Immunohistochemical analysis displayed mPGES-1 was expressed in the outermost layer of the peritoneal membrane and upregulated in peritoneal tissue of patients with peritoneal ultrafiltration failure. In cultured human mesothelial cells, high glucose time-dependently increased the expression of mPGES-1. Western blots confirmed that mPGES-1 was increased more than threefold by high glucose. Besides, application of mPGES-1 shRNA plasmid significantly reduced protein and mRNA expressions of mPGES-1 in human mesothelial cells. Moreover, inhibition of mPGES-1 in human mesothelial cells dramatically reversed levels of E-cadherin and decreased the synthesis of MMT-related proteins, such as fibronectin and vimentin.
Conclusion
The findings suggest that mPGES-1 could be activated by high glucose and could contribute to MMT of PMC.