Expression profiling of genes related to asthma exacerbations

Expression profiling of genes related to asthma exacerbations
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DOI:
10.1111/j.1365-2222.2008.03186.x
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发表时间:
2009-02-01
影响因子:
6.1
通讯作者:
Noguchi, E.
Noguchi, E.
中科院分区:
医学2区
文献类型:
--
作者:
Aoki, T.;Matsumoto, Y.;Noguchi, E.

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背景 哮喘是一种慢性气道炎症性疾病。然而,哮喘急性发作的分子机制尚不完全清楚。 目的 为了鉴定反映哮喘急性发作的基因表达特征,我们通过微阵列分析检测哮喘急性发作和稳定状态期间基因的差异表达。 方法 研究对象为对螨敏感的哮喘儿童和非哮喘对照儿童。这些儿童被分为四组(AE:哮喘恶化,n = 12;SA:哮喘稳定,n = 11;IC:感染对照,n = 6;NC:非感染对照,n = 5)。从外周血单核细胞中提取总 RNA,并使用 Illumina Human Ref8 BeadChip 阵列进行微阵列分析。韦尔奇的 t 检验是为了识别在哮喘恶化期间表达发生改变的基因。对43名哮喘儿童和11名对照儿童采集的样本进行实时定量RT-PCR以验证微阵列结果。结果通过微阵列分析评估哮喘恶化期间137/16基因的表达显着上调/下调。其中 62 个基因在上呼吸道感染期间也有差异表达。许多哮喘发作相关基因参与防御反应和对外部刺激的反应,但在排除感染相关基因后,这些关联消失了。定量实时 RT-PCR 证实,与感染相关的基因(S100A8 和 GAS6)和与感染无关的基因(CD200 和 RBP7)在哮喘恶化期间存在差异表达(P
Background Asthma is a chronic airway inflammatory disease; however, the molecular mechanisms that underlie asthma exacerbation are only partially understood.Objective To identify gene expression signatures that reflect the acute exacerbation of asthma, we examined the differential expression of genes during asthma exacerbation and stable condition by using microarray analysis.Methods The subjects were mite-sensitive asthmatic children and non-asthmatic control children. The children were divided into four groups (AE: asthma exacerbation, n = 12; SA: stable asthma, n = 11; IC: infected control, n = 6; and NC: non-infected control, n = 5). Total RNA was extracted from peripheral blood mononuclear cells and subjected to microarray analysis with Illumina Human Ref8 BeadChip arrays. Welch's t-test was performed to identify genes whose expression was altered during asthma exacerbation. Quantitative real-time RT-PCR was performed on samples collected from 43 asthmatic children and 11 control children to verify the microarray results.Results The expression of 137/16 genes was significantly up/down-regulated during asthma exacerbation assessed by microarray analysis. Of the genes, 62 were also differentially expressed during upper respiratory infection. Many of the asthma exacerbation related genes were involved in defence responses and responses to external stimuli, but these associations disappeared after excluding the infection-related genes. Quantitative real-time RT-PCR confirmed that the genes related (S100A8 and GAS6) and unrelated to infections (CD200 and RBP7) were differentially expressed during asthma exacerbation (P