Airway Secretory microRNAome Changes during Rhinovirus Infection in Early Childhood.
Airway Secretory microRNAome Changes during Rhinovirus Infection in Early Childhood.
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DOI：
10.1371/journal.pone.0162244
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Nino G
中科院分区：
文献类型：
--
作者：
Gutierrez MJ;Gomez JL;Perez GF;Pancham K;Val S;Pillai DK;Giri M;Ferrante S;Freishtat R;Rose MC;Preciado D;Nino G
先天免疫反应是由被称为microRNAs(MiRs)的非编码小RNA分子微调的，它根据环境的反应改变基因表达。在急性感染期间，miRs可以在细胞外小泡(EV)中分泌，以促进细胞间的遗传通讯。这项研究的目的是描述幼儿呼吸道EV(呼吸道分泌型microRNAome)分泌的miRs的基线种群，并检测鼻病毒(RV)感染期间的变化，RV是哮喘恶化的最常见原因，也是儿童以后哮喘发展的最重要的早期危险因素。鼻腔分泌物取自3岁儿童(≤)。在PCR确认的轮状病毒感染期间(n=10)和年龄匹配的对照组(n=10)。使用基于聚合物的沉淀法和使用纳米串微阵列生成的全球miR图谱来分离鼻腔EV。我们使用在气液界面(ALI)分化的原代人支气管上皮细胞(HBEC)的顶端分泌物，在体外呼吸道上皮模型中验证了我们的体内呼吸道分泌物miR数据。生物信息学工具被用来确定统一的(鼻腔和支气管)特征的呼吸道分泌miRNAome和儿童轮状病毒感染期间的变化。多尺度分析确定了由基础呼吸道分泌型miRNAome组成的4个标志性miR：hsa-miR-630、hsa-miR-302d-3p、hsa-miR-320E、hsa-miR-612。我们确定hsa-miR-155是幼儿RV感染期间基线miRNAome的主要变化。我们使用来自实验性活体人类轮状病毒感染的基因数据集的电子模型，研究了hsa-mir-155呼吸道分泌物的潜在生物学相关性。这些分析证实，hsa-miR-155靶点组是轮状病毒感染者上呼吸道中过度表达的途径。对儿童呼吸道分泌性microRNAome的比较分析表明，RV感染与含有miR-155的EV的呼吸道分泌有关，Silico预测miR-155可调节抗病毒免疫。健康和疾病期间呼吸道分泌型microRNAome的进一步特征可能导致治疗和监测所有年龄段的呼吸疾病的全新策略。
Innate immune responses are fine-tuned by small noncoding RNA molecules termed microRNAs (miRs) that modify gene expression in response to the environment. During acute infections, miRs can be secreted in extracellular vesicles (EV) to facilitate cell-to-cell genetic communication. The purpose of this study was to characterize the baseline population of miRs secreted in EVs in the airways of young children (airway secretory microRNAome) and examine the changes during rhinovirus (RV) infection, the most common cause of asthma exacerbations and the most important early risk factor for the development of asthma beyond childhood. Nasal airway secretions were obtained from children (≤3 yrs. old) during PCR-confirmed RV infections (n = 10) and age-matched controls (n = 10). Nasal EVs were isolated with polymer-based precipitation and global miR profiles generated using NanoString microarrays. We validated our in vivo airway secretory miR data in an in vitro airway epithelium model using apical secretions from primary human bronchial epithelial cells (HBEC) differentiated at air-liquid interface (ALI). Bioinformatics tools were used to determine the unified (nasal and bronchial) signature airway secretory miRNAome and changes during RV infection in children. Multiscale analysis identified four signature miRs comprising the baseline airway secretory miRNAome: hsa-miR-630, hsa-miR-302d-3p, hsa- miR-320e, hsa-miR-612. We identified hsa-miR-155 as the main change in the baseline miRNAome during RV infection in young children. We investigated the potential biological relevance of the airway secretion of hsa-mir-155 using in silico models derived from gene datasets of experimental in vivo human RV infection. These analyses confirmed that hsa-miR-155 targetome is an overrepresented pathway in the upper airways of individuals infected with RV. Comparative analysis of the airway secretory microRNAome in children indicates that RV infection is associated with airway secretion of EVs containing miR-155, which is predicted in silico to regulate antiviral immunity. Further characterization of the airway secretory microRNAome during health and disease may lead to completely new strategies to treat and monitor respiratory conditions in all ages.
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影响因子：
6.4
作者：
Cheng, Yong Q.;Ren, Jun P.;Yao, Zhi Q.
通讯作者：
Yao, Zhi Q.
DOI：
10.1165/rcmb.2013-0396oc
发表时间：
2014-09-01
影响因子：
6.4
作者：
Alcala, Sarah E.;Benton, Angela S.;Freishtat, Robert J.
通讯作者：
Freishtat, Robert J.
DOI：
10.1164/rccm.200603-392oc
发表时间：
2006-11-15
影响因子：
24.7
作者：
Kicic, Anthony;Sutanto, Erika N.;Stick, Stephen M.
通讯作者：
Stick, Stephen M.
影响因子：
6.1
作者：
Kim, Y. -S.;Choi, E. -J.;Kim, Y. -K.
通讯作者：
Kim, Y. -K.
影响因子：
3.7
作者：
Graff JW;Powers LS;Dickson AM;Kim J;Reisetter AC;Hassan IH;Kremens K;Gross TJ;Wilson ME;Monick MM
通讯作者：
Monick MM