Enhanced Bronchial Expression of Extracellular Matrix Proteins in Chronic Obstructive Pulmonary Disease

Abstract

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 beta2 in patients with COPD (forced expiratory volume in 1 second [FEV1] <or=75%; n = 15) and without COPD (FEV1 >or=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 beta2 (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.

Reticular basement membrane in asthma and COPD: Similar thickness, yet different composition

“…Kranenburg and colleagues compared the staining intensity of the RBM in patients with COPD and healthy subjects in surgical resection specimens using a similar scoring system as in our study. 49 Their results showed enhanced expression of total collagen, collagen I, and -III, but not of collagen IV, fi bronectin, and laminin. Differences with our fi ndings are likely caused by the use of surgical resection specimens whereas we investigated large airway bronchoscopic biopsies.…”

Annexin A2 mediates collagen VI secretion, pulmonary elasticity, and bronchial epithelial cell apoptosis

“…Polarized epithelial cells, such as those in the lung, continuously remodel the basement membrane by secreting and proteolyzing its component proteins; in turn, basement membrane proteins support epithelial cell-adhesion, survival and differentiation (Pozzi and Zent, 2011). Alterations in basement membrane composition accompany an array of human lung disorders, including asthma, chronic obstructive pulmonary disease and interstitial fibrosis (Cox and Erler, 2011;Kranenburg et al, 2006;Lambrecht and Hammad, 2012;Proud and Leigh, 2011).…”

Circulating fibronectin to C-reactive protein ratio and mortality: a biomarker in COPD?

“…Although the local lung expression of fibronectin is usually increased [32], systemic (circulating) levels are, paradoxically, decreased in COPD [33]. The reduced levels are associated with increased symptoms and severity of disease [33].…”