Identification of microRNAs associated with ileal and colonic Crohn's disease.

Identification of microRNAs associated with ileal and colonic Crohn's disease.
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DOI:
10.1002/ibd.21267
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发表时间:
2010-10
影响因子:
4.9
通讯作者:
Kwon, John H.
Kwon, John H.
中科院分区:
医学2区
文献类型:
--
作者:
Wu, Feng;Zhang, Simin;Dassopoulos, Themistocles;Harris, Mary L.;Bayless, Theodore M.;Meltzer, Stephen J.;Brant, Steven R.;Kwon, John H.

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克罗恩病(CD)和溃疡性结肠炎(UC)与免疫功能、伤口愈合和组织重塑相关的基因表达差异有关。Micro-RNAs(MiRNAs)是一种小的、非编码的RNAs,它作为基因表达的强有力的负调控因子,在包括UC在内的慢性炎症性疾病中差异表达。我们研究了miRNAs在不同肠段组织以及回肠和结肠CD活动期患者中的表达。取正常健康成人的末端回肠、盲肠、横结肠、乙状结肠和直肠,以及回肠和结肠CD活动期患者的回肠和乙状结肠,进行结肠镜夹层活检。用miRNA芯片检测miRNA的表达,并用成熟的miRNA定量逆转录聚合酶链式反应(RT-PCR)进行验证。共鉴定出10个肠道区域特异性miRNAs。与结肠相比,回肠末端有3个miRNA增加,1个miRNA减少。另外六个miRNAs在结肠区表达水平不同。与正常对照组相比,5个miRNAs在活动期结肠CD患者的组织中差异表达,其中3个增加,2个减少。同样,4个miRNAs在活动期回肠CD患者的组织中显著增加。回肠CD、结肠CD和先前发现的UC相关miRNAs之间的表达差异支持miRNAs影响每个炎症性肠病(IBD)亚型中不同炎症相关基因表达的可能性,并可能形成未来IBD诊断测试和治疗靶点的基础。
Crohn’s disease (CD) and ulcerative colitis (UC) are associated with expression differences in genes involved in immune function, wound healing, and tissue remodeling. Micro-RNAs (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.
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期刊: Science (New York, N.Y.)
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