DNA去甲基化在溃疡性结肠炎发病机制中的作用研究

Ulcerative colitis (UC) represents the major subphenotype of the inflammatory bowel disease (IBD). To compare with the healthy individuals, numerous significant differently methylated genomic regions or losi were detected in the affected mucosa from UC patient, furthermore, most of the aberrations are hypomethylation, and associate with inflammation. It suggested that DNA demethylation might play a very impotant role in the progress and manifestation of UC. But it is still unknown about the epigenetic differences between UC and acute colitis. We validated some significant down methylated candidates with the affected mucosa from the acute colitis patients and UC patients, and we found that the intermediate product of DNA demethylation - - - - hydroxymethylation are significant higher in acute colitis than in UC. In the following project, we would focus on the difference and relationship of these two kinds of demethylation between UC and acute colitis on the genome-wide scale and investigate their potential regulatory mechanisms.

溃疡性结肠炎是炎症性肠病的主要亚型之一。相对健康人，在溃疡性结肠炎患者的受累肠粘膜当中发现了很多显著异常甲基化的染色组区域或者位点，而且，这些异常甲基化多表现为降低，并和炎症相关。这暗示，DNA去甲基化过程可能在溃疡性结肠炎这一疾病的发生发展和表现上有重要作用。但是，溃疡性结肠炎和其他急性结肠炎之间的表观遗传学差异仍是未知。我们在急性结肠炎患者的受累肠粘膜中验证了几个显著低甲基化染色组区间和位点，我们发现DNA去甲基化的中间产物- - - - 羟甲基化程度在急性结肠炎中显著高于溃疡性结肠炎。在本项目中，我们将在全基因组范围内关注两种去甲基化模式在溃疡性结肠炎和急性结肠炎之间的区别和联系，并研究它们潜在的调控机理，为进一步理解两类炎症在表观遗传学上的病理机理提供依据。