Effect of DNA Demethylation in Experimental Encapsulating Peritoneal Sclerosis

Kyung Hoon Kim, Hye Myung Ryu, Se Hyun Oh, Eun Joo Oh, Ji Sun Ahn, Jong Hak Lee, Ji Young Choi, Jang Hee Cho, Chan Duck Kim, Yong Lim Kim, Sun Hee Park

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Encapsulating peritoneal sclerosis (EPS) involves excessive peritoneal fibrosis in patients on peritoneal dialysis, eventually leading to visceral constriction and bowel obstruction. Few studies have investigated epigenetic mechanisms relating to EPS. Here we evaluated the therapeutic effects of DNA demethylation in experimental EPS. Experimental EPS was induced by intraperitoneal injection of 0.1% chlorhexidine gluconate (CG) and 15% ethanol in non-uremic male Sprague-Dawley (SD) rats. Rats were divided into three groups: group C (N=5) with saline injection only, group CG (N=7) with EPS induction for 4weeks, and chlorhexidine gluconate and azacytidine (CGA) treated group (N=7) with EPS induction for 4weeks and 5'-azacytidine injection for the last 2weeks. Morphometric analysis of peritoneum and immunohistochemical staining for type 1 collagen and α-smooth muscle actin (α-SMA) were performed. Expressions of transforming growth factor-β (TGF-β), fibroblast-specific protein 1 (FSP1), and DNA methyltransferase 1 (DNMT1) were analyzed by Western blot. Methylation-specific polymerase chain reaction (PCR) for Ras GTPase activating-like protein 1 (RASAL1) was performed with measurement of RASAL1 protein expression. Parietal peritoneal thickness and the number of vessels in omental tissue were significantly decreased in group CGA compared to group CG, as were the expressions of type 1 collagen, α-SMA, TGF-β, and FSP1. DNMT1 was significantly increased in group CG, and reduced in group CGA. RASAL1 hypermethylation was associated with decreased RASAL1 protein expression in group CG, which was reversed in group CGA. DNA demethylation by 5'-azacytidine treatment improved pathologic changes of the peritoneum in experimental EPS, and was associated with reversal of increased DNMT1 expression and RASAL1 hypermethylation.

Original languageEnglish
Pages (from-to)628-636
Number of pages9
JournalTherapeutic Apheresis and Dialysis
Volume18
Issue number6
DOIs
StatePublished - 1 Dec 2014

Keywords

  • DNA demethylation
  • Encapsulating peritoneal sclerosis
  • Peritoneal dialysis
  • Peritoneal fibrosis

Fingerprint

Dive into the research topics of 'Effect of DNA Demethylation in Experimental Encapsulating Peritoneal Sclerosis'. Together they form a unique fingerprint.

Cite this