Department of Medicine, Section of Gastroenterology, University of Chicago, Chicago, Illinois 60637, USA.
Inflamm Bowel Dis. 2010 Oct;16(10):1729-38. doi: 10.1002/ibd.21267.
Crohn's disease (CD) and ulcerative colitis (UC) are associated with expression differences in genes involved in immune function, wound healing, and tissue remodeling. MicroRNAs (miRNAs) are small, noncoding RNAs that act as potent negative regulators of gene expression and are differentially expressed in chronic inflammatory diseases, including UC. We examined the expression of miRNAs in tissues from different intestinal regions and in patients with active ileal and colonic CD.
Colonoscopic pinch biopsies were obtained from the terminal ileum, cecum, transverse colon, sigmoid colon, and rectum of normal, healthy adults and from the ileum and sigmoid colon of patients with active ileal and colonic CD. miRNA expression was assessed using miRNA microarray and validated by mature miRNA quantitative reverse-transcription polymerase chain reaction (RT-PCR).
Ten intestine region-specific miRNAs were identified. Three miRNAs were increased and one miRNA was decreased in the terminal ileum as compared to the colon. Six other miRNAs expressed varying levels of expression among the colon regions. Five miRNAs were found to be differentially expressed in tissues of patients with active colonic CD, with three increased and two decreased as compared to normal, healthy controls. Similarly, four miRNAs were found to be significantly increased in tissues of patients with active ileal CD.
The expression differences between ileal CD, colonic CD, and previously identified UC-associated miRNAs support the likelihood that miRNAs influence differing inflammation-related gene expression in each inflammatory bowel disease (IBD) subtype and may form the basis for future diagnostic tests and therapeutic targets for IBD.
克罗恩病(CD)和溃疡性结肠炎(UC)与涉及免疫功能、伤口愈合和组织重塑的基因表达差异有关。microRNAs(miRNAs)是小的非编码 RNA,作为基因表达的有效负调节剂,在包括 UC 在内的慢性炎症性疾病中表达不同。我们检查了来自不同肠道区域的组织和活动回肠和结肠 CD 患者中 miRNA 的表达。
从正常健康成年人的末端回肠、盲肠、横结肠、乙状结肠和直肠以及活动性回肠和结肠 CD 患者的回肠和乙状结肠获得结肠镜夹活检。使用 miRNA 微阵列评估 miRNA 表达,并通过成熟 miRNA 定量逆转录聚合酶链反应(RT-PCR)进行验证。
确定了 10 个肠道区域特异性 miRNA。与结肠相比,末端回肠中有 3 个 miRNA 增加,1 个 miRNA 减少。另外 6 个 miRNA 在结肠区域表达不同水平的表达。在活动性结肠 CD 患者的组织中发现 5 个 miRNA 表达差异,与正常健康对照相比,有 3 个增加,2 个减少。同样,在活动性回肠 CD 患者的组织中发现 4 个 miRNA 显著增加。
回肠 CD、结肠 CD 之间的表达差异以及先前确定的与 UC 相关的 miRNA 支持 miRNA 影响每种炎症性肠病(IBD)亚型中不同炎症相关基因表达的可能性,并且可能为未来的诊断测试和 IBD 治疗靶点奠定基础。