Airway epithelial miRNA expression is altered in asthma

Am J Respir Crit Care Med. 2012 Nov 15;186(10):965-74. doi: 10.1164/rccm.201201-0027OC. Epub 2012 Sep 6.


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 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.

Conclusions: 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 (NCT 00595153).

Trial registration: NCT00595153.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adult
  • Asthma / drug therapy
  • Asthma / genetics
  • Asthma / metabolism*
  • Bronchi / drug effects
  • Bronchi / metabolism*
  • Budesonide / administration & dosage
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Female
  • Glucocorticoids / administration & dosage
  • Humans
  • Interleukin-13 / pharmacology
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • MicroRNAs / physiology
  • Microarray Analysis
  • Polymerase Chain Reaction


  • Glucocorticoids
  • Interleukin-13
  • MicroRNAs
  • Budesonide

Associated data