Abstract
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.
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Abbreviations
- EMT:
-
Epithelial-to-mesenchymal transition
- AGEs:
-
Advanced glycation end products
- FBS:
-
Fetal bovine serum
- PVDF:
-
Polyvinylidene fluoride
- Nrf2:
-
Nucleus factor erythroid 2-related factor 2
- HPMCs:
-
Human peritoneal mesothelial cells
- DMSO:
-
Solubilization solution dimethyl sulfoxide
- ROS:
-
Reactive oxygen species
- PD:
-
Peritoneal fibrosis
- HO-1:
-
Oxygenase-1
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Acknowledgements
I need to thank Academician Chen Xiangmei, Associate professor of medicine Li Qinggang and Supervisor nurse Zhou lili for their thoughts and insights on the design of our research and their contributions to the successful completion of this research.
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XF and LM designed the study, wrote and revised the manuscript. XF, WS, ZZ and YH conducted the experiment. XF contributed the data collection and data analysis. XF and LM revised the manuscript. All our authors carefully read and clearly approved the final manuscript.
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Xiao Fenglin, Wang Shengyuan, Zhang Zhiyong, Yu Hai and Li Mingxu declare that there are not any commercial, financial or associative interest that represents a conflict of interest in connection with the manuscript entitled “Pirfenidone ameliorated AGEs induced EMT and attenuated peritoneal fibrosis in peritoneal mesothelial cells”.
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Fenglin, X., Shengyuan, W., Zhiyong, Z. et al. Pirfenidone ameliorated AGE-induced EMT and attenuated peritoneal fibrosis in peritoneal mesothelial cells. Mol. Cell. Toxicol. 17, 315–323 (2021). https://doi.org/10.1007/s13273-021-00138-5
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DOI: https://doi.org/10.1007/s13273-021-00138-5