Expression of the genes dual oxidase 2, lipocalin 2 and regenerating islet-derived 1 alpha in Crohn's disease
Expression of the genes dual oxidase 2, lipocalin 2 and regenerating islet-derived 1 alpha in Crohn's disease
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DOI：
10.1080/00365520600976266
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发表时间：
2007-04-01
影响因子：
1.9
通讯作者：
Borup, Rehannah
中科院分区：
文献类型：
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作者：
Csillag, Claudio;Nielsen, Ole Haagen;Borup, Rehannah
Objective.对来自克罗恩病（CD）患者的非炎症结肠粘膜细胞和来自对照组的结肠粘膜细胞进行了整体基因表达谱分析。材料和方法。从33名CD患者和17名对照受试者中通过结肠镜获得肉眼可见的非炎症降结肠组织标本。所有对照组和10例CD患者在结肠镜检查时均未服药。使用人类基因组U133 Plus 2.0基因芯片阵列进行基因分析。用dChip软件分析杂交数据。结果通过实时逆转录聚合酶链反应（RT-PCR）证实。使用Envision +可视化技术通过免疫组织化学评估所选基因的蛋白产物表达。结果采用统计学临界点设置时，表达谱不均匀。与对照组比较，发现19例CD患者有三个差异表达基因，其中两个与先天免疫系统有关：15号染色体上的双氧化酶2（DUOX 2，倍数变化4.1）和9号染色体上的脂质运载蛋白2（LCN 2，倍数变化3.1）。第三个基因，再生胰岛衍生1 α（REG 1A，倍数变化3.9），编码促有丝分裂蛋白;这不能通过RT-PCR证实。与对照组相比，无药物治疗的患者没有差异表达的基因。免疫组化结果表明，这些蛋白质由上皮细胞（REGIA，LCN 2）和白细胞（DUOX 2和LCN 2）产生。结论.与对照组相比，非炎症结肠粘膜细胞含有两个与先天免疫系统相关的上调基因。已知这些基因的上调是由微生物诱导的，这表明微生物抗原性增加或粘膜屏障防御功能改变。
Objective. A global gene expression profile of non-inflamed colonic mucosal cells from patients with Crohn's disease (CD) and of colonic mucosal cells from controls was performed. Material and methods. Tissue specimens from macroscopically non-inflamed descending colon were obtained colonoscopically from 33 CD patients and from 17 control subjects. All controls and 10 CD patients were medication-free at the time of colonoscopy. The Human Genome U133 Plus 2.0 GeneChip Array was used for gene profiling. Hybridization data were analysed with dChip software. Results were confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Protein product expression of selected genes was assessed by immunohistochemistry using the Envision + visualization technique. Results. The expression profile was not homogeneous with the statistical cut-point settings applied. In comparison with controls, it was found that19 CD patients had three differentially expressed genes, two of them related to the innate immune system: dual oxidase 2 on chromosome 15 (DUOX2, fold change 4.1) and lipocalin 2 on chromosome 9 (LCN2, fold change 3.1). The third gene, regenerating islet-derived 1 alpha (REG1A, fold change 3.9), codes for a mitogenic protein; this could not be confirmed by RT-PCR. Medication-free patients had no differentially expressed genes as compared with controls. Immunohistochemistry indicated that these proteins were produced by epithelial cells (REGIA, LCN2) and leucocytes (DUOX2 and LCN2). Conclusions. As compared with controls, non-inflamed colonic mucosal cells contain two up-regulated genes related to the innate immune system. Up-regulation of these genes, known to be induced by microorganisms, suggests either increased microflora antigenicity or an altered function in mucosal barrier defence.