Inflammation-associated DNA methylation patterns in epithelium of ulcerative colitis

Aberrant DNA methylation patterns have been reported in inflamed tissues and may play a role in disease. We studied DNA methylation and gene expression profiles of purified intestinal epithelial cells from ulcerative colitis patients, comparing inflamed and non-inflamed areas of the colon. We identified 577 differentially methylated sites (false discovery rate PRAC1 and PRAC2. Four genes showed inverse correlation between methylation and gene expression; ROR1, GXYLT2, FOXA2, and, notably, RARB, a gene previously identified as a tumor suppressor in colorectal adenocarcinoma as well as breast, lung and prostate cancer. We highlight targeted and specific patterns of DNA methylation and gene expression in epithelial cells from inflamed colon, while challenging the importance of epithelial cells in the pathogenesis of chronic inflammation.

已有研究证实，炎症组织中存在异常DNA甲基化（DNA methylation）模式，且该模式可能参与疾病的发生发展过程。本研究针对溃疡性结肠炎（ulcerative colitis）患者的纯化肠道上皮细胞，开展了DNA甲基化与基因表达谱（gene expression profiles）分析，并对比了结肠炎症区域与非炎症区域的差异。本研究共鉴定出577个差异甲基化位点（differentially methylated sites），其错误发现率（false discovery rate）相关参数涉及PRAC1与PRAC2。其中4个基因的甲基化水平与基因表达量呈负相关，依次为ROR1、GXYLT2、FOXA2，尤为值得关注的是RARB——该基因此前被证实为结直肠腺癌（colorectal adenocarcinoma）以及乳腺癌、肺癌、前列腺癌中的抑癌基因。本研究着重揭示了炎症结肠上皮细胞中特异性的DNA甲基化与基因表达模式，同时对肠道上皮细胞在慢性炎症（chronic inflammation）发病机制（pathogenesis）中的重要性提出了质疑。