Airway Epithelial miRNA Expression Is Altered in Asthma

作者：Owen D. Solberg, Edwin Justin Ostrin, Michael I. Love, Jeffrey C. Peng, Nirav R. Bhakta, Lydia Hou, Christine Nguyen, Margaret Solon, Cindy N. Nguyen, Andrea J. Barczak, Lorna T. Zlock, Denitza Blagev, Walter E. Finkbeiner, Karl Mark Ansel, Joseph R. Arron, David J. Erle, Prescott G. Woodruff · 发表于：American Journal of Respiratory and Critical Care Medicine · 年份：2012 · DOI：10.1164/rccm.201201-0027oc · 被引用次数：246 · 研究领域：MicroRNA in disease regulation、Asthma and respiratory diseases、Extracellular vesicles in disease

RATIONALE: Changes in airway epithelial cell differentiation, driven in part by IL-13, are important in asthma. Micro-RNAs (miRNAs) regulate cell differentiation in many systems and could contribute to epithelial abnormalities in asthma. OBJECTIVES: To determine whether airway epithelial miRNA expression is altered in asthma and identify IL-13-regulated miRNAs. METHODS: We used miRNA microarrays to analyze bronchial epithelial brushings from 16 steroid-naive subjects with asthma before and after inhaled corticosteroids, 19 steroid-using subjects with asthma, and 12 healthy control subjects, and the effects of IL-13 and corticosteroids on cultured bronchial epithelial cells. We used quantitative polymerase chain reaction to confirm selected microarray results. MEASUREMENTS AND MAIN RESULTS: Most (12 of 16) steroid-naive subjects with asthma had a markedly abnormal pattern of bronchial epithelial miRNA expression by microarray analysis. Compared with control subjects, 217 miRNAs were differentially expressed in steroid-naive subjects with asthma and 200 in steroid-using subjects with asthma (false discovery rate < 0.05). Treatment with inhaled corticosteroids had modest effects on miRNA expression in steroid-naive asthma, inducing a statistically significant (false discovery rate < 0.05) change for only nine miRNAs. qPCR analysis confirmed differential expression of 22 miRNAs that were highly differentially expressed by microarrays. IL-13 stimulation recapitulated changes in ma...