Epithelial expression of profibrotic mediators in a model of allergen-induced airway remodeling.
Airway remodeling, including subepithelial fibrosis, is a characteristic feature of asthma and likely contributes to the pathogenesis of airway hyperresponsiveness. We examined expression of genes related to airway wall fibrosis in a model of chronic allergen-induced airway dysfunction using laser capture microdissection and quantitative real-time PCR. BALB/c mice were sensitized and subjected to chronic ovalbumin exposure over a 12-wk period, after which they were rested and then harvested 2 and 8 wk after the last exposure. Chronic allergen-exposed mice had significantly increased indices of airway remodeling and airway hyperreactivity at all time points, although no difference in expression of fibrosis-related genes was found when mRNA extracted from whole lung was examined. In contrast, fibrosis-related gene expression was significantly upregulated in mRNA obtained from microdissected bronchial wall at 2 wk after chronic allergen exposure. In addition, when bronchial wall epithelium and smooth muscle were separately microdissected, gene expression of transforming growth factor-beta1 and plasminogen activating inhibitor-1 were significantly upregulated only in the airway epithelium. These data suggest that transforming growth factor-beta1 and other profibrotic mediators produced by airway wall, and specifically, airway epithelium, play an important role in the pathophysiology of airway remodeling.
Kelly
Margaret M
MM
Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, MDCL-4017, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.
Leigh
Richard
R
Bonniaud
Philippe
P
Ellis
Russ
R
Wattie
Jennifer
J
Smith
Mary Jo
MJ
Martin
Gail
G
Panju
Mohammed
M
Inman
Mark D
MD
Gauldie
Jack
J
D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001980:Bronchi / Q000378:metabolism / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D010047:Ovalbumin / Q000008:administration & dosage; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D053773:Transforming Growth Factor beta1
D000485:Allergens; D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D010047:Ovalbumin