Abstract: SA-PO942
The Global DNA Methylation Profile of Human Peritoneal Fibrosis
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
Authors
- Yan, Pengpeng, Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Hangzhou, ZHEJIANG, China
- Shen, Jia, Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Hangzhou, ZHEJIANG, China
- Wang, Rending, Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Hangzhou, ZHEJIANG, China
- Chen, Jianghua, Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Hangzhou, ZHEJIANG, China
Background
Long-term exposure to biocompatible peritoneal dialysate induced peritoneum fibrosis, exacerbating peritoneal dialysis (PD) efficiency.
Methods
Peritoneal tissues of PD patients were obtained during kidney transplantation (PD group, n=10), along with Control group from normal individuals (n=6). Histological staining and qRT-PCR were applied to evaluate the peritoneal fibrosis level, while Infinium® HumanMethylation EPIC was used to analyze differentially methylated probes (DMPs), which formed the gene clusters ( corrected p<0.05, |Δβ|>0.2). Functional network analysis was applied to extract the key regions within the interaction.
Results
Structural remodeling was found in Peritoneum from PD patients, including SMC significant thickening, vascular wall of peritoneal postcapillary venules thickening (p<0.001). The number of α-SMA positive cells in PD peritoneum increased, with up-regulation of Fibronectin and Vimentin mRNA (p<0.05).
The global DNA methylation level decreased in PD peritoneum, with 9,948 up-regulated DMPs and 39,109 down-regualed DMPs, which covered all euchromosome and were enriched in function or pathway terms such as cell morphology, cell migration, and ECM buildup; functional analysis of the CpG-rich regions revealed THBS1 and PRKACA are two key functional blocks related to cell proliferation/migration, which involved Wnt/β-catenin signaling pathway and PKA signaling pathway, respectively.
Conclusion
Fibrotic structural remodeling was presented in the peritoneum of PD patients, with a hypomethylated reprogramming of the global DNA methylation profile.
Funding
- Government Support - Non-U.S.