title: MicroRNA-19a enhances proliferation of bronchial epithelial cells by targeting TGFβR2 gene in severe asthma.
abstract: BACKGROUND
  Allergic asthma is characterized by inflammation and airway remodeling. Bronchial epithelium is considered a key player in coordinating airway wall remodeling. In mild asthma, the epithelium is damaged and fails to proliferate and to repair, whereas in severe asthma, the epithelium is highly proliferative and thicker. This may be due to different regulatory mechanisms. The purpose of our study was to determine the role of miRNAs in regulating proliferation of bronchial epithelial cells obtained from severe asthmatic subjects in comparison with cells obtained from mild asthmatics and healthy controls.
  
  
  METHODS
  Human bronchial epithelial cells (BEC) were isolated by bronchoscopy from bronchial biopsies of healthy donors and patients with mild and severe asthma. MiRNA expression was evaluated using the TaqMan low-density arrays and qRT-PCR. Transfection studies of bronchial epithelial cells were performed to determine the target genes. Cell proliferation was evaluated by BrdU incorporation test.
  
  
  RESULTS
  MiR-19a was upregulated in epithelia of severe asthmatic subjects compared with cells from mild asthmatics and healthy controls. Functional studies based on luciferase reporter and Western blot assays suggest that miR-19a enhances cell proliferation of BEC in severe asthma through targeting TGF-β receptor 2 mRNA. Moreover, repressed expression of miR-19a increased SMAD3 phosphorylation through TGF-β receptor 2 signaling and abrogated BEC proliferation.
  
  
  CONCLUSIONS
  Our study uncovers a new regulatory pathway involving miR-19a that is critical to the severe phenotype of asthma and indicates that downregulating miR-19a expression could be explored as a potential new therapy to modulate epithelium repair in asthma.
authors.affiliation: Centre de recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, Québec, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Haj-Salem
authors.forename: R
authors.initials: R
authors.lastname: Fakhfakh
authors.forename: J-C
authors.initials: JC
authors.lastname: Bérubé
authors.forename: E
authors.initials: E
authors.lastname: Jacques
authors.forename: S
authors.initials: S
authors.lastname: Plante
authors.forename: M J
authors.initials: MJ
authors.lastname: Simard
authors.forename: Y
authors.initials: Y
authors.lastname: Bossé
authors.forename: J
authors.initials: J
authors.lastname: Chakir
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D001249:Asthma / Q000175:diagnosis / Q000235:genetics*; D001706:Biopsy; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D005541:Forced Expiratory Volume; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D012720:Severity of Illness Index; D051900:Smad3 Protein / Q000378:metabolism; D013183:Sputum / Q000166:cytology; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; C549214:MIRN19A microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D051900:Smad3 Protein; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II
keywords: TGF-β receptor 2; epithelial cells; microRNA; severe asthma