Interferon regulatory factor 7 is a major hub connecting interferon-mediated responses in virus-induced asthma exacerbations in vivo.
Interferon regulatory factor 7 is a major hub connecting interferon-mediated responses in virus-induced asthma exacerbations in vivo.
复制标题
DOI：
10.1016/j.jaci.2011.10.038
复制
发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
Martinez FD
中科院分区：
文献类型：
--
作者：
Bosco A;Ehteshami S;Panyala S;Martinez FD
急性发作是造成儿童哮喘发病率和医疗保健利用的重大负担。大多数哮喘加重是由病毒感染引起的，然而，其潜在机制尚未得到系统的研究。本研究的目的是阐明在哮喘儿童体内支持病毒诱导的恶化的分子网络。我们前瞻性地跟踪了易加重的哮喘儿童，并分析了急性、中度、小核糖核酸病毒引起的加重以及7-14天后鼻腔灌洗液样本中基因表达的整体模式。利用共表达网络分析和先验知识来重建潜在的基因网络。数据显示，与7-14天后相比，一个由1000多个基因组成的复杂模块化程序在急性加重期间上调。这些模块被丰富用于一致的细胞过程，包括干扰素诱导的抗病毒反应、先天病原体感知、对损伤的反应、小核仁rna、泛素-蛋白体和溶酶体降解途径。这些模块的接线图重建显示了超连接枢纽节点的存在，最值得注意的是IRF7，它被确定为连接干扰素介导的抗病毒反应的主要枢纽。本研究提供了在体内病毒诱导的哮喘恶化期间上调的炎症网络的综合观点。一系列先天信号中枢被确定为哮喘发作的新治疗靶点。
Exacerbations are responsible for a substantial burden of morbidity and health care utilization in children with asthma. Most asthma exacerbations are triggered by viral infections, however, the underlying mechanisms have not been systematically investigated. The objective of this study was to elucidate the molecular networks that underpin virus-induced exacerbations in asthmatic children in vivo. We followed exacerbation-prone asthmatic children prospectively, and profiled global patterns of gene expression in nasal lavage samples obtained during an acute, moderate, Picornavirus-induced exacerbation, and 7–14 days later. Coexpression network analysis and prior knowledge was employed to reconstruct the underlying gene networks. The data showed that an intricate, modular program consisting of more than one thousand genes was upregulated during acute exacerbations, in comparison to 7–14 days later. The modules were enriched for coherent cellular processes, including interferon-induced antiviral responses, innate pathogen sensing, response to wounding, small nucleolar RNAs, and the ubiquitin-proteosome and lysosome degradation pathways. Reconstruction of the wiring diagram of the modules revealed the presence of hyper-connected hub nodes, most notably IRF7, which was identified as a major hub linking interferon-mediated antiviral responses. This study provides an integrated view of the inflammatory networks that are upregulated during virus-induced asthma exacerbations in vivo. A series of innate signalling hubs were identified that could be novel therapeutic targets for asthma attacks.
登录
查看更多内容
DOI：
10.1038/nri2851
发表时间：
2010-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
8
作者：
通讯作者：
--
DOI：
10.1126/science.1179050
发表时间：
2009-10-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Amit I;Garber M;Chevrier N;Leite AP;Donner Y;Eisenhaure T;Guttman M;Grenier JK;Li W;Zuk O;Schubert LA;Birditt B;Shay T;Goren A;Zhang X;Smith Z;Deering R;McDonald RC;Cabili M;Bernstein BE;Rinn JL;Meissner A;Root DE;Hacohen N;Regev A
通讯作者：
Regev A
DOI：
10.1165/rcmb.2004-0417oc
发表时间：
2006-02-01
影响因子：
6.4
作者：
Chen, Y;Hamati, E;Wu, R
通讯作者：
Wu, R