Identification of gene networks and pathways associated with Guillain-Barré syndrome.

Identification of gene networks and pathways associated with Guillain-Barré syndrome.
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DOI:
10.1371/journal.pone.0029506
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Chen CM
Chen CM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chang KH;Chuang TJ;Lyu RK;Ro LS;Wu YR;Chang HS;Huang CC;Kuo HC;Hsu WC;Chu CC;Chen CM

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吉兰-巴雷综合征(GBS)基因网络表达的潜在变化仍然是难以捉摸的。我们试图通过分析GBS患者白细胞的转录谱来确定GBS相关的基因网络和信号通路。对7例GBS患者和7例健康对照者的外周血白细胞进行了定量基因表达微阵列分析。在标准化后比较患者和对照之间的基因表达谱。通过免疫途径分析进一步分析与GBS显著相关的基因集。256个基因和18个基因网络与GBS显著相关(倍数变化≥2,P<0.05)。FOS、PTGS 2、HMGB 2和MMP 9是246个显著上调基因中的前4个。与GBS相关的最重要的疾病和生物学功能改变的基因是那些涉及炎症反应、感染性疾病和呼吸系统疾病的基因。细胞死亡、细胞发育和细胞运动是GBS最重要的分子和细胞功能。血液系统发育和功能、免疫细胞运输和生物体存活是生理发育和系统类别中最重要的GBS相关功能。在相关基因网络中发现了几个枢纽基因,如MMP 9、PTGS 2和CREB 1。经典通路分析表明,GnRH、促肾上腺皮质激素释放激素和ERK/MAPK信号通路是GBS中上调表达基因组中最重要的通路。这项研究揭示了与GBS相关的基因网络和经典途径。这些数据不仅为理解GBS的致病特性提供了基因之间的网络,而且还为未来开发新的治疗策略绘制了重要的途径。
The underlying change of gene network expression of Guillain-Barré syndrome (GBS) remains elusive. We sought to identify GBS-associated gene networks and signaling pathways by analyzing the transcriptional profile of leukocytes in the patients with GBS. Quantitative global gene expression microarray analysis of peripheral blood leukocytes was performed on 7 patients with GBS and 7 healthy controls. Gene expression profiles were compared between patients and controls after standardization. The set of genes that significantly correlated with GBS was further analyzed by Ingenuity Pathways Analyses. 256 genes and 18 gene networks were significantly associated with GBS (fold change ≥2, P<0.05). FOS, PTGS2, HMGB2 and MMP9 are the top four of 246 significantly up-regulated genes. The most significant disease and altered biological function genes associated with GBS were those involved in inflammatory response, infectious disease, and respiratory disease. Cell death, cellular development and cellular movement were the top significant molecular and cellular functions involved in GBS. Hematological system development and function, immune cell trafficking and organismal survival were the most significant GBS-associated function in physiological development and system category. Several hub genes, such as MMP9, PTGS2 and CREB1 were identified in the associated gene networks. Canonical pathway analysis showed that GnRH, corticotrophin-releasing hormone and ERK/MAPK signaling were the most significant pathways in the up-regulated gene set in GBS. This study reveals the gene networks and canonical pathways associated with GBS. These data provide not only networks between the genes for understanding the pathogenic properties of GBS but also map significant pathways for the future development of novel therapeutic strategies.
DOI: 10.1002/ana.410400414
发表时间: 1996-10-01
影响因子: 11.2
作者:
HaferMacko, C;Hsieh, ST;Griffin, JW
通讯作者: Griffin, JW
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期刊: ENDOCRINOLOGY
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发表时间: 1996-01-01
影响因子: 11.2
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DOI: 10.1038/sj.emboj.7600309
发表时间: 2004-08-04
期刊: EMBO JOURNAL
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作者:
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