Critical COPD respiratory illness is linked to increased transcriptomic activity of neutrophil proteases genes.
Critical COPD respiratory illness is linked to increased transcriptomic activity of neutrophil proteases genes.
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DOI：
10.1186/1756-0500-5-401
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发表时间：
2012-08-02
影响因子：
1.8
通讯作者：
Bermejo-Martin, Jesus F
中科院分区：
文献类型：
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作者：
Almansa, Raquel;Socias, Lorenzo;Bermejo-Martin, Jesus F
背景：从外周血获得的细胞中的基因表达谱（GEP）表明，这是发现生物标志物和研究流行疾病分子发病机制的非常有用的方法。虽然与慢性阻塞性肺疾病 (COPD) 相关的基因表达标记物的文献有限，但目前尚不清楚与该疾病中的严重呼吸系统疾病相关的转录组图谱。 结果：通过使用安捷伦微阵列芯片，我们分析了 28 名因不同程度的呼吸系统损害而住院的 COPD 患者全血中的基因表达特征。其中 12 人需要入住 ICU，16 人入住呼吸内科服务中心。使用GeneSpring GX 11.0软件对ICU和非ICU患者之间的转录水平进行统计比较。 Ingenuity 通路分析 8.5 (IPA) 和京都基因和基因组百科全书 (KEGG) 用于按功能和通路（基因本体论）选择、注释和可视化基因。 T 检验显示 ICU 和非 ICU 患者之间有 1501 个基因存在差异表达。对最具代表性的生物学功能的IPA和KEGG分析显示，ICU患者的中性粒细胞基因转录物水平升高，包括[组织蛋白酶G（CTSG）]、[弹性蛋白酶，中性粒细胞表达（ELANE）]、[蛋白酶3（PRTN3）]、[髓过氧化物酶（MPO）]、[组织蛋白酶D（CTSD）]、[防御素，α3，中性粒细胞特异性(DEFA3)]、azurocidin 1 (AZU1)]和[杀菌/通透性增加蛋白(BPI)]是最具代表性的。这些基因编码的蛋白质形成中性粒细胞嗜天青颗粒的一部分，并参与抗菌防御和组织损伤。这种“中性粒细胞特征”与高级呼吸和生命支持的必要性以及细菌感染的存在并行。结论：血液中转录组特征的研究表明，中性粒细胞蛋白酶在患有严重呼吸系统疾病的慢性阻塞性肺病患者中发挥着重要作用。这些基因表达的测量和调节可以为临床监测和治疗慢性阻塞性肺病严重恶化提供一种选择。
BACKGROUND: Gene expression profiling (GEP) in cells obtained from peripheral blood has shown that this is a very useful approach for biomarker discovery and for studying molecular pathogenesis of prevalent diseases. While there is limited literature available on gene expression markers associated with Chronic Obstructive Pulmonary Disease (COPD), the transcriptomic picture associated with critical respiratory illness in this disease is not known at the present moment.FINDINGS: By using Agilent microarray chips, we have profiled gene expression signatures in the whole blood of 28 COPD patients hospitalized with different degrees of respiratory compromise.12 of them needed of admission to the ICU, whilst 16 were admitted to the Respiratory Medicine Service. GeneSpring GX 11.0 software was used for performing statistical comparisons of transcript levels between ICU and non-ICU patients. Ingenuity pathway analysis 8.5 (IPA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to select, annotate and visualize genes by function and pathway (gene ontology). T-test showed evidence of 1501 genes differentially expressed between ICU and non-ICU patients. IPA and KEGG analysis of the most representative biological functions revealed that ICU patients had increased levels of neutrophil gene transcripts, being [cathepsin G (CTSG)], [elastase, neutrophil expressed (ELANE)], [proteinase 3 (PRTN3)], [myeloperoxidase (MPO)], [cathepsin D (CTSD)], [defensin, alpha 3, neutrophil-specific (DEFA3)], azurocidin 1 (AZU1)], and [bactericidal/permeability-increasing protein (BPI)] the most representative ones. Proteins codified by these genes form part of the azurophilic granules of neutrophils and are involved in both antimicrobial defence and tissue damage. This "neutrophil signature" was paralleled by the necessity of advanced respiratory and vital support, and the presence of bacterial infection.CONCLUSION: Study of transcriptomic signatures in blood suggests an essential role of neutrophil proteases in COPD patients with critical respiratory illness. Measurement and modulation of the expression of these genes could present an option for clinical monitoring and treatment of severe COPD exacerbations.