MicroRNAs Expression in the Ileal Pouch of Patients with Ulcerative Colitis is Robustly Up-Regulated and Correlates with Disease phenotypes. Homo sapiens

Gene expression alterations are associated with disease behavior in inflammatory bowel disease (IBD). microRNAs (miRNAs) are dominant in the regulation of gene expression, and may affect IBD phenotype. Our aim was to assess mucosal miRNA expression in IBD and the correlation with intestinal inflammation. Sixty-one subjects were recruited. The ileum of unoperated UC patients was comparable with NC. There were significant miRNA expression alterations (fold change ≥2, corrected P ≤.05) in NP (n = 6), CP (n = 40) and CLDP (n = 139), but only two expression alterations were noted in CD. More than 90% of the altered miRNAs were up-regulated, and many were predicted to be associated with significantly decreased transcripts. miRNAs alterations were generally clustered with disease phenotypes. Ileal inflammation causes increased miRNA expression. miRNA alterations correlate with IBD phenotype, apparently by controlling the down-regulation of specific mRNAs. Overall design: Pouchitis is a model for ileal Inflammatory Bowel Disease (IBD) and may enable the detection of miRNAs associated with intestinal inflammation. Control/disease samples: Crohn's-like disease of the pouch (CLDP), chronic pouchitis (CP-P), Ileal Crohn's disease (IlealCD), normal control (NC), normal pouch (NP-P), ulcerative colitis (UC).

基因表达改变与炎症性肠病（inflammatory bowel disease, IBD）的疾病行为密切相关。微小RNA（microRNAs，miRNAs）在基因表达调控中占据主导地位，可影响IBD表型。本研究旨在评估IBD患者黏膜组织的miRNA表达水平，及其与肠道炎症的相关性。本研究共招募61名受试者。未接受手术的溃疡性结肠炎（ulcerative colitis, UC）患者的回肠组织与正常对照（normal control, NC）无显著差异。在正常储袋（NP, n=6）、慢性储袋炎（CP, n=40）及储袋克罗恩样病变（Crohn's-like disease of the pouch, CLDP, n=139）中均检测到显著的miRNA表达改变（倍数变化≥2，校正P值≤0.05），而回肠克罗恩病（Ileal Crohn's disease, IlealCD）中仅观察到2处表达改变。超过90%的差异表达miRNAs呈上调趋势，且其中多数被预测可与显著下调的转录本相关联。miRNA表达改变通常与疾病表型聚类相关。回肠炎症可导致miRNA表达水平升高。miRNA表达改变与IBD表型显著相关，其机制可能通过调控特定mRNA的下调实现。
整体实验设计：储袋炎（pouchitis）可作为回肠炎症性肠病的模型，有助于检测与肠道炎症相关的miRNAs。对照/疾病样本包括：储袋克罗恩样病变（CLDP）、慢性储袋炎（CP-P）、回肠克罗恩病（IlealCD）、正常对照（NC）、正常储袋（NP-P）及溃疡性结肠炎（UC）。