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Pirfenidone ameliorated AGE-induced EMT and attenuated peritoneal fibrosis in peritoneal mesothelial cells
Molecular & Cellular Toxicology  (IF1.08),  Pub Date : 2021-05-17, DOI: 10.1007/s13273-021-00138-5
Xiao Fenglin, Wang Shengyuan, Zhang Zhiyong, Yu Hai, Li Mingxu

Background

Peritoneal dialysis has greatly improved patient survival for patients with chronic kidney disease. However, peritoneal fibrosis is a progressive fibrotic peritoneal disease caused by dialysis, which may lead to ineffective dialysis or dialysis failure. It is well known that the EMT of peritoneal mesenchymal cells has been known to contribute to peritoneal fibrosis. Therefore, at present, inhibiting the formation and development of EMT has become the focus of peritoneal fibrosis.

Objectives

Pirfenidone has shown clinically relevant benefits in patients with pulmonary fibrosis, however, there is no research on peritoneal fibrosis. Thus, we examined the effect of pirfenidone on AGE-driven EMT in peritoneal mesenchymal cells and assessed its efficacy in inhibiting peritoneal fibrosis.

Results

AGEs were added with or without pirfenidone to the culture medium of HMrSV5 cells and we detected the changes of EMT and the signaling pathways involved. AGEs greatly reduced the E-cadherin level and augmented the α–SMA and vimentin expression. However, these effects were dramatically suppressed by pirfenidone treatment. Meanwhile, the reactive oxygen species (ROS) induced by AGEs were suppressed by pirfenidone. Furthermore, under the action of AGEs, pirfenidone activated the nuclear transport of Nrf2, and accelerated the production of antioxidant factors.

Conclusion

Pirfenidone could attenuate AGE-mediated EMT in HPMCs and might be a promising therapeutic drug to antagonize peritoneal fibrosis.