Divisione di Pneumologia e Laboratorio di Citoimmunopatologia dell'Apparato Cardio Respiratorio, Istituti Clinici Scientifici Maugeri, SpA, Società Benefit, IRCCS, Veruno (NO), Italy.
Divisione di Pneumologia e Laboratorio di Citoimmunopatologia dell'Apparato Cardio Respiratorio, Istituti Clinici Scientifici Maugeri, SpA, Società Benefit, IRCCS, Veruno (NO), Italy.
Chest. 2018 Apr;153(4):851-862. doi: 10.1016/j.chest.2017.12.017. Epub 2017 Dec 28.
The expression and localization of transforming growth factor-β (TGF-β) pathway proteins in different compartments of the lower airways of patients with stable COPD is unclear. We aimed to determine TGF-β pathway protein expression in patients with stable COPD.
The expression and localization of TGF-β pathway components was measured in the bronchial mucosa and peripheral lungs of patients with stable COPD (n = 44), control smokers with normal lung function (n = 24), and control nonsmoking subjects (n = 11) using immunohistochemical analysis.
TGF-β1, TGF-β3, and connective tissue growth factor expression were significantly decreased in the bronchiolar epithelium, with TGF-β1 also decreased in alveolar macrophages, in patients with stable COPD compared with control smokers with normal lung function. TGF-β3 expression was increased in the bronchial lamina propria of both control smokers with normal lung function and smokers with mild/moderate stable COPD compared with control nonsmokers and correlated significantly with pack-years of smoking. However, TGF-β3 cells decreased in patients with severe/very severe COPD compared with control smokers. Latent TGF-β binding protein 1 expression was increased in the bronchial lamina propria in subjects with stable COPD of all severities compared with control smokers with normal lung function. Bone morphogenetic protein and activin membrane-bound inhibitor expression (BAMBI) in the bronchial mucosa was significantly increased in patients with stable COPD of all severities compared with control subjects. No other significant differences were observed between groups for all the other molecules studied in the bronchial mucosa and peripheral lung.
Expression of TGF-βs and their regulatory proteins is distinct within different lower airway compartments in stable COPD. Selective reduction in TGF-β1 and enhanced BAMBI expression may be associated with the increase in autoimmunity in COPD.
转化生长因子-β（TGF-β）通路蛋白在稳定期 COPD 患者下呼吸道不同部位的表达和定位尚不清楚。我们旨在确定稳定期 COPD 患者中 TGF-β 通路蛋白的表达。
采用免疫组织化学分析方法，检测 44 例稳定期 COPD 患者、24 例肺功能正常的吸烟对照者和 11 例非吸烟对照者支气管黏膜和外周肺组织中 TGF-β 通路成分的表达和定位。
与肺功能正常的吸烟对照者相比，稳定期 COPD 患者的小气道上皮细胞中 TGF-β1、TGF-β3 和结缔组织生长因子表达显著降低，肺泡巨噬细胞中 TGF-β1 也降低。TGF-β3 表达在肺功能正常的吸烟对照者和轻度/中度稳定期 COPD 吸烟者的支气管固有层均增加，与吸烟包年数显著相关。然而，与肺功能正常的吸烟对照者相比，严重/极严重 COPD 患者的 TGF-β3 细胞减少。与肺功能正常的吸烟对照者相比，所有严重程度的稳定期 COPD 患者的支气管固有层中潜伏 TGF-β 结合蛋白 1 表达增加。所有严重程度的稳定期 COPD 患者的支气管黏膜中骨形态发生蛋白和激活素膜结合抑制剂（BAMBI）表达均显著增加。在支气管黏膜和外周肺组织中，其他研究的分子在各组之间未观察到其他显著差异。
在稳定期 COPD 患者的不同下呼吸道部位，TGF-βs 及其调节蛋白的表达存在差异。TGF-β1 的选择性减少和 BAMBI 表达的增强可能与 COPD 中自身免疫的增加有关。
