Microarray analysis identifies an aberrant expression of apoptosis and DNA damage-regulatory genes in multiple sclerosis
Microarray analysis identifies an aberrant expression of apoptosis and DNA damage-regulatory genes in multiple sclerosis
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DOI：
10.1016/j.nbd.2004.10.007
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发表时间：
2005-04-01
影响因子：
6.1
通讯作者：
Yamamura, T
中科院分区：
文献类型：
--
作者：
Satoh, J;Nakanishi, M;Yamamura, T
为了阐明多发性硬化(MS)促进自身免疫过程的分子机制，我们用基因芯片技术研究了72例MS患者和22例年龄和性别匹配的健康对照(CN)外周血单个核细胞(PBMC)中T细胞和非T细胞部分的基因表达谱。在检测的1258个基因中，有173个在MS组和CN组之间在T细胞和50个非T细胞中有差异表达。在MS中，下调基因的数量远远多于上调基因的数量，在前30个最重要的基因中，超过80%的基因被归类为促凋亡和抗凋亡两类与凋亡信号相关的基因。其中包括孤儿核受体Nurr1(NR4A2)、受体相互作用丝氨酸/苏氨酸激酶2(RIPK2)和死亡结构域沉默蛋白(SODD)的表达上调，肿瘤坏死因子相关的凋亡诱导配体(TRAIL)、B细胞CLL/淋巴瘤2(BCL2)和死亡相关蛋白6(DAXX)的表达下调。此外，一组参与DNA修复、复制和染色质重塑的基因在MS中下调。这些结果表明，MS淋巴细胞表现出一种复杂的基因调控模式，代表着促进和防止淋巴细胞凋亡和DNA损伤之间的平衡。(C)2004 Elsevier Inc.保留所有权利。
To clarify the molecular mechanisms underlying multiple sclerosis (MS)-promoting autoimmune process, we have investigated a comprehensive gene expression profile of T cell and non-T cell fractions of peripheral blood mononuclear cells (PBMC) isolated from 72 MS patients and 22 age- and sex-matched healthy control (CN) subjects by using a cDNA microarray. Among 1258 genes examined, 173 genes in T cells and 50 genes in non-T cells were expressed differentially between MS and CN groups. Downregulated genes greatly outnumbered upregulated genes in MS. More than 80% of the top 30 most significant genes were categorized into apoptosis signaling-related genes of both proapoptotic and antiapoptotic classes. They included upregulation in MS of orphan nuclear receptor Nurr1 (NR4A2), receptor-interacting serine/threonine kinase 2 (RIPK2), and silencer of death domains (SODD), and downregulation in MS of TNF-related apoptosis-inducing ligand (TRAIL), B-cell CLL/lymphoma 2 (BCL2), and death-associated protein 6 (DAXX). Furthermore, a set of the genes involved in DNA repair, replication, and chromatin remodeling was downregulated in MS. These results suggest that MS lymphocytes show a complex pattern of gene regulation that represents a counterbalance between promoting and preventing apoptosis and DNA damage of lymphocytes. (c) 2004 Elsevier Inc. All rights reserved.