The relationship between airway remodeling and transforming growth factor-beta1 and basic fibroblast growth factor expression in bronchoalveolar lavage cells from asthmatics

Kim, Seung Joon; Lee, Sook Young; Park, Yong Keun; Kim, Myung Hoon; Kim, Seok Chan; Kwon, Soon Seog; Kim, Young Kyoon; Kim, Kwan Hyoung; Moon, Hwa Sik; Song, Jeong Sup; Park, Sung Hak

Abstract

BACKGROUND AND OBJECTIVE: Airway wall remodeling such as epithelial shedding, increased basement membrane thickness, subepithelial fibrosis is established pathological features in asthma. However the pathogenesis of this structural alteration is not well understood. In other chronic inflammatory diseases, fibrotic change occurs usually and the growth factor for fibroblast is particulary important. Our purpose was to study whether transforming growth factor-beta1 (TGF- beta1) and basic fibroblast growth factor (bFGF) were related to airway remodeling.
METHODS
In asthmatics (n=24) and non-asthma controls (n=4), epithelial shedding and basement membrane thickness were measured by hematoxylin-eosin stain and the degree of subepithelial fibrosis was measured by Masson-trichrome stain. TGF- beta1 and bFGF positive cells were measured in BAL fluid by immunocytochemical stain using monoclonal antibody.
RESULTS
Epithelial shedding (20.00 +/- 11.55% vs 49.77 +/- 30.80%, P<0.01) and basement membrane thickness (8.25 +/- 2.63 micrometer vs 13.50 +/- 4.36 micrometer, P<0.05) were significantly increased in asthmatics than controls. And the degree of subepithelial fibrosis in asthmatics had increased tendency as compared with controls (52.5 +/- 12.56 micrometer vs 117.05 +/- 63.73 micrometer, P=0.06). The degree of epithelial shedding was significantly increased in severe asthmatics as compared with controls, mild and moderate asthmatics (31.25 +/- 26.96% vs 65.42 +/- 27.59%, P<0.05) and basement membrane thickness was significantly increased in moderate, severe asthmatics as compared with controls (8.25 +/- 2.63 micrometer vs 14.50 +/- 4.85 micrometer, P<0.05) but the degree of subepithelial fibrosis according to clinical severity was statistically insignificant. TGF- beta1 expression in asthmatics was significantly higher than control group (0.00 +/- 0.00% vs 13.13 +/- 22.35%, P<0.05), and bFGF expression had increased tendency in asthmatics but statistically insignificant. There was no significant correlation between the degree of basement membrane thickness, subepithelial fibrosis and TGF- beta1 or bFGF expression in BAL cells from asthmatics. Severity of asthma, duration of asthma, FEV1, and PC20 were not correlated with TGF- beta1 or bFGF expression.
CONCLUSION
We showed that bronchial epithelial shedding, basement membrane thickening and subepithelial fibrosis were observed in asthmatics, and the expression of TGF- beta1 was increased in asthmatics. These results suggested that TGF- beta1 might be related to the airway remodeling. But the direct correlation between TGF- beta1 or bFGF expression in BAL cells and the degree of airway remodeling was not observed. Further studies on other growth factors, TGF- beta1 and bFGF expression in bronchial mucosal tissue and time sequence of cytokine expression on airway remodeling should be needed.