6533b834fe1ef96bd129cb04

RESEARCH PRODUCT

Pro-and anti-fibrotic molecule balance in the bronchial mucosa of stable COPD patients

subject

description

Background: The mechanisms of inducing fibrotic events and remodeling in the airways of COPD are incompletely studied. Objectives: To investigate the expression of cytokines involved in the pro- and anti-fibrotic events in stable COPD. Methods: Expression of CTGF, TGFβ1-2-3, TGFβRI, TGFβRII, LTBP-1, TRAP-1, BAMBI, PP2Cα, Smad2-3-6-7, pSmad2, pSmad3, pro-collagen-I and collagen-I was measured in the bronchial mucosa using immunohistochemistry and RT-qPCR. Results: TGFβ1 was increased in the epithelium and TGFβ3 in the submucosa of healthy smokers and mild/moderate COPD compared to healthy non-smokers. In all smokers and patients with COPD TGFβ3+ cells in the submucosa correlated significantly with pack/years. BAMBI was higher in epithelium and submucosa of mild/moderate and severe/very-severe COPD compared to control smokers and non-smokers. RT-qPCR confirmed increased levels of TGFβ3 mRNA in healthy smokers and BAMBI mRNA in mild/moderate and severe/very-severe COPD. BAMBI immunoexpression was higher in the epithelium of all COPD when compared to age matched asthmatics and it correlated inversely with the thickness of the reticular basement membrane in all COPD and control subjects. No significant differences were observed in the immunoexpression of CTGF, TGFβ2, TGFβRI, TGFβRII, Smad2-3-6-7, pSmad2, pSmad3, PP2Cα, TRAP-1, pro-collagen-I and collagen-I. In vitro, TGFβ1 treatment of 16HBE cells up-regulated mRNA BAMBI expression. Conclusion: Bronchial increased expression of the anti-fibrotic TGFβ pseudoreceptor BAMBI in COPD, together with no changes of pro-fibrotic molecules demonstrates an imbalance of these molecules with a prevalence of an anti-fibrotic pattern in COPD of increasing severity.