小RNA
表观遗传学
生物信息学
痰
生物
微阵列
炎症
吸入
吸入染毒
微阵列分析技术
免疫系统
免疫学
基因表达
医学
基因
遗传学
病理
肺结核
解剖
作者
Rebecca C. Fry,Julia E. Rager,Rebecca N. Bauer,Elizabeth Sebastian,David B. Peden,Ilona Jaspers,Neil E. Alexis
出处
期刊:American Journal of Physiology-lung Cellular and Molecular Physiology
[American Physiological Society]
日期:2014-06-15
卷期号:306 (12): L1129-L1137
被引量:84
标识
DOI:10.1152/ajplung.00348.2013
摘要
Ozone (O 3 ) is a criteria air pollutant that is associated with numerous adverse health effects, including altered respiratory immune responses. Despite its deleterious health effects, possible epigenetic mechanisms underlying O 3 -induced health effects remain understudied. MicroRNAs (miRNAs) are epigenetic regulators of genomic response to environmental insults and unstudied in relationship to O 3 inhalation exposure. Our objective was to test whether O 3 inhalation exposure significantly alters miRNA expression profiles within the human bronchial airways. Twenty healthy adult human volunteers were exposed to 0.4 ppm O 3 for 2 h. Induced sputum samples were collected from each subject 48 h preexposure and 6 h postexposure for evaluation of miRNA expression and markers of inflammation in the airways. Genomewide miRNA expression profiles were evaluated by microarray analysis, and in silico predicted mRNA targets of the O 3 -responsive miRNAs were identified and validated against previously measured O 3 -induced changes in mRNA targets. Biological network analysis was performed on the O 3 -associated miRNAs and mRNA targets to reveal potential associated response signaling and functional enrichment. Expression analysis of the sputum samples revealed that O 3 exposure significantly increased the expression levels of 10 miRNAs, namely miR-132, miR-143, miR-145, miR-199a*, miR-199b-5p, miR-222, miR-223, miR-25, miR-424, and miR-582-5p. The miRNAs and their predicted targets were associated with a diverse range of biological functions and disease signatures, noted among them inflammation and immune-related disease. The present study shows that O 3 inhalation exposure disrupts select miRNA expression profiles that are associated with inflammatory and immune response signaling. These findings provide novel insight into epigenetic regulation of responses to O 3 exposure.
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