Abstract: SA-PO941
Genetic or Pharmacologic Blockade of Enhancer of Zeste Homolog 2 Inhibits the Progression of Peritoneal Fibrosis
Session Information
- Peritoneal Dialysis: Inflammation, Peritoneal Transport
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 703 Dialysis: Peritoneal Dialysis
Authors
- Liu, Na, shanghai east hospital, Shanghai, China
- Shi, Yingfeng, Nephrology department Shanghai Dongfang Hospital, Shanghai, SHANGHAI, China
- Qiu, Andong, Tongji University, Shanghai, SHANGHAI, China
- Zhuang, Shougang, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, United States
Background
Dysregulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in many cancers. However, the role of EZH2 in peritoneal fibrosis remains unknown.
Methods
We investigated EZH2 expression in peritoneal dialysis (PD) patients and assessed its role in peritoneal fibrosis induced by chlorhexidine gluconate (CG) or high glucose peritoneal dialysis fluid (PDF) in mice by using 3-deazaneplanocin A (3-DZNeP), and EZH2 conditional knockout mice in fibroblasts.
Results
An abundance of EZH2 was detected in the peritoneum of patients with PD associated peritonitis and the dialysis effluent of long-term PD patients. EZH2 was also highly expressed in the peritoneum of mice after injury by CG or PDF, and treatment with 3-DZNeP attenuated peritoneal fibrosis and inhibited activation of several pro-fibrotic mechanisms. Moreover, delayed administration of 3-DZNeP inhibited peritoneal fibrosis progression, reversed established peritoneal fibrosis and reduced matrix metalloproteinases-2 (MMP-2) and MMP-9 expression. Finally, EZH2-KO mice exhibited less peritoneal fibrosis compared with EZH2-WT mice. In cultured peritoneal mesothelial cells, EZH2 inhibition resulted in suppression of α-SMA and Collagen I and preservation of E-cadherin.
Conclusion
These results indicate that EZH2 is a key epigenetic regulator that promotes peritoneal fibrosis. Targeting EZH2 may have the potential to prevent and treat peritoneal fibrosis.