Airway Epithelial miRNA Expression Is Altered in Asthma

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. To determine whether airway epithelial miRNA expression is altered in ast...

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Bibliographic Details
Published in:American journal of respiratory and critical care medicine 2012-11, Vol.186 (10), p.965-974
Main Authors: SOLBERG, Owen D, OSTRIN, Edwin J, ZLOCK, Lorna T, BLAGEV, Denitza P, FINKBEINER, Walter E, ANSEL, K. Mark, ARRON, Joseph R, ERLE, David J, WOODRUFF, Prescott G, LOVE, Michael I, PENG, Jeffrey C, BHAKTA, Nirav R, HOU, Lydia, NGUYEN, Christine, SOLON, Margaret, NGUYEN, Cindy, BARCZAK, Andrea J
Format: Article
Language:English
Subjects:
Administration, Inhalation
Adult
Airway management
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Arrays
Asthma
Asthma - drug therapy
Asthma - genetics
Asthma - metabolism
Biological and medical sciences
Bronchi - drug effects
Bronchi - metabolism
Budesonide - administration & dosage
Cells, Cultured
Dose-Response Relationship, Drug
Emergency and intensive respiratory care
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Female
Gene expression
Glucocorticoids - administration & dosage
Humans
Intensive care medicine
Interleukin-13 - pharmacology
Male
Medical sciences
Microarray Analysis
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
MicroRNAs - physiology
Polymerase Chain Reaction
Signal transduction
Steroids
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Summary: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. To determine whether airway epithelial miRNA expression is altered in asthma and identify IL-13-regulated miRNAs. 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. 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 many differentially expressed miRNAs, including four members of the miR-34/449 family, and these changes in miR-34/449 family members were resistant to corticosteroids. Dramatic alterations of airway epithelial cell miRNA levels are a common feature of asthma. These alterations are only modestly corrected by inhaled corticosteroids. IL-13 effects may account for some of these alterations, including repression of miR-34/449 family members that have established roles in airway epithelial cell differentiation. Clinical trial registered with www.clinicaltrials.gov (NCT 00595153).
ISSN:1073-449X
1535-4970
DOI:10.1164/rccm.201201-0027oc