title: Airway epithelial miRNA expression is altered in asthma.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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 www.clinicaltrials.gov (NCT 00595153).
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Owen D
authors.initials: OD
authors.lastname: Solberg
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Ostrin
authors.forename: Michael I
authors.initials: MI
authors.lastname: Love
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Peng
authors.forename: Nirav R
authors.initials: NR
authors.lastname: Bhakta
authors.forename: Lydia
authors.initials: L
authors.lastname: Hou
authors.forename: Christine
authors.initials: C
authors.lastname: Nguyen
authors.forename: Margaret
authors.initials: M
authors.lastname: Solon
authors.forename: Cindy
authors.initials: C
authors.lastname: Nguyen
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Barczak
authors.forename: Lorna T
authors.initials: LT
authors.lastname: Zlock
authors.forename: Denitza P
authors.initials: DP
authors.lastname: Blagev
authors.forename: Walter E
authors.initials: WE
authors.lastname: Finkbeiner
authors.forename: K Mark
authors.initials: KM
authors.lastname: Ansel
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Arron
authors.forename: David J
authors.initials: DJ
authors.lastname: Erle
authors.forename: Prescott G
authors.initials: PG
authors.lastname: Woodruff
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism*; D019819:Budesonide / Q000008:administration & dosage; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D046228:Microarray Analysis; D016133:Polymerase Chain Reaction
chemical_list: D005938:Glucocorticoids; D018793:Interleukin-13; D035683:MicroRNAs; D019819:Budesonide