Department of Medicine, Section of Gastroenterology, University of Chicago, Chicago, Illinois 60637, USA.
Inflamm Bowel Dis. 2011 Jan;17(1):241-50. doi: 10.1002/ibd.21450. Epub 2010 Sep 1.
Crohn's disease (CD) and ulcerative colitis (UC) result from pathophysiologically distinct dysregulated immune responses, as evidenced by the preponderance of differing immune cell mediators and circulating cytokine expression profiles. MicroRNAs (miRNAs) are small, noncoding RNAs that act as negative regulators of gene expression and have an increasingly recognized role in immune regulation. We hypothesized that differences in circulating immune cells in CD and UC patients are reflected by altered miRNA expression and that miRNA expression patterns can distinguish CD and UC from normal healthy individuals.
Peripheral blood was obtained from patients with active CD, inactive CD, active UC, inactive UC, and normal healthy adults. Total RNA was isolated and miRNA expression assessed using miRNA microarray and validated by mature miRNA quantitative reverse-transcription polymerase chain reaction.
Five miRNAs were significantly increased and two miRNAs (149* and miRplus-F1065) were significantly decreased in the blood of active CD patients as compared to healthy controls. Twelve miRNAs were significantly increased and miRNA-505* was significantly decreased in the blood of active UC patients as compared to healthy controls. Ten miRNAs were significantly increased and one miRNA was significantly decreased in the blood of active UC patients as compared to active CD patients.
Peripheral blood miRNAs can be used to distinguish active CD and UC from healthy controls. The data support the evidence that CD and UC are associated with different circulating immune cells types and that the differential expression of peripheral blood miRNAs may form the basis of future diagnostic tests for inflammatory bowel disease.
克罗恩病(CD)和溃疡性结肠炎(UC)是由病理生理学上不同的免疫失调反应引起的,这一点可以从不同的免疫细胞介质和循环细胞因子表达谱的优势中得到证明。microRNAs(miRNAs)是一种小的非编码 RNA,作为基因表达的负调控因子,在免疫调节中具有越来越被认可的作用。我们假设 CD 和 UC 患者循环免疫细胞的差异反映在 miRNA 表达的改变上,并且 miRNA 表达模式可以将 CD 和 UC 与正常健康个体区分开来。
从活动期 CD 患者、缓解期 CD 患者、活动期 UC 患者、缓解期 UC 患者和正常健康成年人中获得外周血。分离总 RNA,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进行验证。
与健康对照组相比,活动期 CD 患者血液中有 5 个 miRNA 显著增加,2 个 miRNA(149和 miRplus-F1065)显著减少。与健康对照组相比,活动期 UC 患者血液中有 12 个 miRNA 显著增加,miRNA-505显著减少。与活动期 CD 患者相比,活动期 UC 患者血液中有 10 个 miRNA 显著增加,1 个 miRNA 显著减少。
外周血 miRNA 可用于区分活动期 CD 和 UC 与健康对照。这些数据支持这样的证据,即 CD 和 UC 与不同的循环免疫细胞类型有关,外周血 miRNA 的差异表达可能为炎症性肠病的未来诊断测试奠定基础。