Underexpression of mitochondrial-DNA encoded ATP synthesis-related genes and DNA repair genes in systemic lupus erythematosus.

Underexpression of mitochondrial-DNA encoded ATP synthesis-related genes and DNA repair genes in systemic lupus erythematosus.
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在全身性红斑狼疮中,线粒体-DNA编码与ATP合成相关基因和DNA修复基因的不渗透。

DOI:
10.1186/ar3317
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发表时间:
2011-04-15
影响因子:
4.9
通讯作者:
Nishimoto N
Nishimoto N
中科院分区:
医学2区
文献类型:
--
作者:
Lee HM;Sugino H;Aoki C;Nishimoto N

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系统性红斑狼疮(SLE)是一种典型的自身免疫性疾病,以多种全身症状和多器官损害为特征。我们通过比较SLE患者与健康个体的基因表达谱,阐明SLE的生物学和功能异常。应用基因芯片技术检测了21例SLE患者和45例健康人外周血基因表达谱。对SLE与健康人差异表达的基因进行基因本体论分析和网络通路分析。共有2,329个上调基因和1,884个下调基因差异表达。基因本体分析表明,上调表达的基因被归类为生物刺激应答基因,其中主要包括与免疫应答相关的基因。在细胞运动和细胞凋亡的调节等方面也发现了异常。下调的基因主要分为两类,感觉知觉和辐射/光反应。感觉基因包括ATP酶/ATP酶结构域基因、肌球蛋白相关基因和两个与DNA修复有关的切除修复交叉互补基因。该组中的其他基因-包括三个晶体蛋白基因,编码黑素细胞刺激激素受体蛋白的基因,以及六个参与ATP合成的DNA编码基因-也被归类为对辐射的反应基因。利用网络通路分析,发现IL-6、转化生长因子β 1、TNF和肝细胞核因子4α在感觉感知相关分子网络中起中心作用。SLE患者外周血细胞ATP合成和DNA修复功能异常
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by various systemic symptoms and multiple organ damage. We clarify biological and functional abnormalities in SLE by comparing the gene expression profiles of SLE patients with those of healthy individuals. Gene expression profiles from the peripheral blood of 21 SLE patients and 45 healthy individuals were obtained using a DNA microarray. Gene ontology analysis and network pathway analysis were performed on the genes differentially expressed between SLE and healthy individuals. A total of 2,329 upregulated genes and 1,884 downregulated genes were differentially expressed. Gene ontology analysis revealed that the upregulated genes were classified as response to biotic stimulus genes, which mainly includes genes related to immune response. Abnormalities in other categories such as cell motility and regulation of apoptosis were also revealed. Downregulated genes were mainly sorted into two gene categories, sensory perception and response to radiation/light. The sensory perception genes included ATPase/ATPase domain-containing genes, myosin-related genes, and two excision repair cross-complementing genes, which are involved in DNA repair. Other genes in this group - including three crystallin genes, genes encoding the receptor protein for melanocyte-stimulating hormone, and six mitochondrial-DNA encoded genes, which are involved in ATP synthesis - were also categorized as response to radiation genes. Using network pathway analysis, IL-6, transforming growth factor beta 1, TNF, and hepatocyte nuclear factor 4α were found to play central roles in the networks of sensory perception-related molecules. Functional abnormalities in ATP synthesis and DNA repair are implicated in peripheral blood cells from SLE patients.
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发表时间: 2008-04
影响因子: 5.3
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Holohan C;Szegezdi E;Ritter T;O'Brien T;Samali A
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期刊: BIOCHIMIE
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影响因子: 13.6
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影响因子: 13.6
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发表时间: 2003-03-17
期刊: The Journal of experimental medicine
影响因子: --
作者:
Bennett L;Palucka AK;Arce E;Cantrell V;Borvak J;Banchereau J;Pascual V
通讯作者: Pascual V