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.

中文翻译：

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吡非尼酮可改善AGE诱导的EMT并减轻腹膜间皮细胞的腹膜纤维化

背景

腹膜透析大大改善了慢性肾脏病患者的生存率。但是，腹膜纤维化是由透析引起的进行性纤维化性腹膜疾病，可能导致无效的透析或透析失败。众所周知，腹膜间充质细胞的EMT有助于腹膜纤维化。因此，目前，抑制EMT的形成和发展已成为腹膜纤维化的重点。

目标

吡非尼酮已在肺纤维化患者中显示出与临床相关的益处，但是，腹膜纤维化尚无研究。因此，我们检查了吡非尼酮对腹膜间充质细胞中AGE驱动的EMT的影响，并评估了其抑制腹膜纤维化的功效。

结果

在含或不含吡非尼酮的AGEs中加入HMrSV5细胞的培养基，我们检测到EMT的变化和涉及的信号通路。AGEs大大降低了E-钙粘蛋白水平，并增加了α-SMA和波形蛋白的表达。然而，吡非尼酮治疗显着抑制了这些作用。同时，吡非尼酮抑制了AGEs诱导的活性氧（ROS）。此外，在AGEs的作用下，吡非尼酮激活了Nrf2的核转运，并加速了抗氧化因子的产生。

结论

吡非尼酮可以减弱HPMCs中AGE介导的EMT，并且可能是拮抗腹膜纤维化的有前途的治疗药物。