Enhanced bronchial expression of extracellular matrix proteins in chronic obstructive pulmonary disease

Enhanced bronchial expression of extracellular matrix proteins in chronic obstructive pulmonary disease
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DOI:
10.1309/jc477fael1ykv54w
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发表时间:
2006-11-01
影响因子:
3.5
通讯作者:
Sharma, Hari S.
Sharma, Hari S.
中科院分区:
医学4区
文献类型:
--
作者:
Kranenburg, Andor R.;Willems-Widyastuti, Anna;Sharma, Hari S.

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气道和血管重塑是慢性阻塞性肺疾病(COPD)的重要特征。通过使用免疫组化分析,我们研究了COPD患者(第一秒用力呼气量[FEV 1] = 85%; n = 16)的各种细胞外基质(ECM)成分(如胶原蛋白(亚型I、III和IV)、纤连蛋白和层粘连蛋白β 2)的支气管表达模式,并将表达数据与肺功能相关。定量分析显示COPD患者表面上皮基底膜(SEBM)中总胶原I、III和IV水平升高(P <0.01),支气管固有层(P <0.02)和外膜(P <0.05)中胶原I和III水平升高。纤连蛋白在血管中的表达明显增加(P <0.05),这是内膜血管纤维化的原因,而层粘连蛋白β 2(P <0.05)在气道平滑肌(ASM)中升高。FEV 1值与SEBM中的胶原蛋白、支气管血管中的纤维连接蛋白和ASM中的层粘连蛋白呈负相关。我们的数据表明,COPD表现出ECM蛋白的支气管沉积增加,导致肺功能恶化和气道重塑。
Remodeling of airways and blood vessels is an important feature in chronic obstructive pulmonary disease (COPD). By using immunohistochemical analysis, we examined bronchial expression patterns of various extracellular matrix (ECM) components such as collagens (subtypes I, III, and IV), fibronectin, and laminin beta 2 in patients with COPD (forced expiratory volume in I second [FEV1] = 85%; n = 16) and correlated expression data with lung function. Quantitative analysis revealed enhanced levels (P < .01) of total collagens I, III, and IV in surface epithelial basement membrane (SEBM) and collagens I and III in bronchial lamina propria (P < .02) and adventitia (P < .05) in COPD. Distinct and increased (P < .05) vascular expression of fibronectin accounts for intimal vascular fibrosis, whereas laminin beta 2 (P < .05) was elevated in airway smooth muscle (ASM). FEV1 values inversely correlated with collagens in the SEBM, fibronectin in bronchial vessels, and laminin in the ASM. Our data suggest that COPD exhibits increased bronchial deposition of ECM proteins that contribute to deteriorated lung function and airway remodeling.