Gastrointestinal Unit, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Inflamm Bowel Dis. 2010 Oct;16(10):1717-28. doi: 10.1002/ibd.21263.
Genome-wide microarray expression analysis creates a comprehensive picture of gene expression at the cellular level. The aim of this study was to investigate differential intestinal gene expression in patients with Crohn's disease (CD) and controls with subanalysis of confirmed CD susceptibility genes, associated pathways, and cell lineage.
In all, 172 biopsies from 53 CD and 31 control subjects were studied. Paired endoscopic biopsies were taken at ileocolonoscopy from five specific anatomical locations including the terminal ileum (TI) for RNA extraction and histology. The 41,058 expression sequence tags were analyzed using the Agilent platform.
Analysis of all CD biopsies versus controls showed 259 sequences were upregulated and 87 sequences were downregulated. Upregulated genes in CD included SAA1 (fold change [FC] +7.5, P = 1.47 × 10(-41)) and REGL (FC +7.3, P = 2.3 × 10(-16)), whereas cellular detoxification genes including-SLC14A2 (FC-2.49, P = 0.00002) were downregulated. In the CD TI biopsies diubiquitin (FC+11.3, P < 1 × 10(-45)), MMP3 (FC+7.4, P = 1.3 × 10(-11)), and IRTA1 (FC-11.4, P = 4.7 × 10(-12)) were differentially expressed compared to controls. In the colon SAA1 (FC+6.3, P = 5.3 × 10(-8)) was upregulated and thymic stromal lymphopoietin (TSLP) (FC-2.3, P = 2.7 × 10(-6)) was downregulated comparing noninflamed CD and control biopsies, and the colonic inflammatory CD signature was characterized by downregulation of the organic solute carriers-SLC38A4, SLC26A2, and OST alpha. Of CD susceptibility genes identified by genome-wide association scan IL-23A, JAK2, and STAT3 were upregulated in the CD group, confirming the dysregulation of Th17 signaling.
These data characterize the dysregulation of a series of specific inflammatory pathways highlighting potential pathogenic mechanisms as well as areas for translation to therapeutic targets.
全基因组微阵列表达分析在细胞水平上创建了基因表达的综合图谱。本研究的目的是研究克罗恩病（CD）患者和对照者的肠道基因表达差异，并对确认的 CD 易感基因、相关途径和细胞谱系进行亚分析。
共研究了 53 例 CD 患者和 31 例对照者的 172 个活检标本。在回结肠镜检查时，从五个特定解剖部位（包括末端回肠 [TI]）采集配对的内镜活检标本，用于提取 RNA 和组织学检查。使用 Agilent 平台分析了 41058 个表达序列标签。
对所有 CD 活检标本与对照者进行分析，发现 259 个序列上调，87 个序列下调。CD 中上调的基因包括 SAA1（倍数变化 [FC] +7.5，P = 1.47×10（-41））和 REGL（FC +7.3，P = 2.3×10（-16）），而细胞解毒基因包括-SLC14A2（FC-2.49，P = 0.00002）下调。在 CD TI 活检标本中，二泛素（FC+11.3，P < 1×10（-45））、MMP3（FC+7.4，P = 1.3×10（-11））和 IRTA1（FC-11.4，P = 4.7×10（-12））与对照者相比差异表达。在结肠中，SAA1（FC+6.3，P = 5.3×10（-8））上调，胸腺基质淋巴细胞生成素（TSLP）（FC-2.3，P = 2.7×10（-6））下调，与非炎症性 CD 和对照活检标本相比，而结肠炎症性 CD 特征是有机溶质载体-SLC38A4、SLC26A2 和 OST alpha 的下调。通过全基因组关联扫描鉴定的 CD 易感基因 IL-23A、JAK2 和 STAT3 在 CD 组中上调，证实了 Th17 信号的失调。
这些数据描述了一系列特定炎症途径的失调，突出了潜在的发病机制以及转化为治疗靶点的领域。
