133 3D lung models – 3D extracellular matrix models an increase in MMPs expression and their enzymatic activity in COPD subjects [36]. Merrilees et al. demonstrated that elastin fibers were decreased in alveoli of COPD lungs [37]. Comparably, immunohistochemical analysis demonstrated a reduction in fractional area of elastic fibers in COPD [38]. Additionally, degradation products of elastin were increased in urinary excretions of COPD patient compared with nonCOPD controls [39]. The destruction of elastin fibers results in loss of lung elasticity, an alteration of the transpulmonary dissemination of the transpulmonary pressure resulting in lung hyperinflation [23]. Additionally, immunohistochemical analyses revealed that the fractional area of type I collagen was significantly reduced in the inner layer and muscle layer of the small airways in COPD when compared with nonsmokers [38]. Interestingly, no changes were reported for other collagens including type III and IV or proteoglycans including decorin, biglycan and lumican [38]. This was in contrast to the findings of van Straaten et al. who reported reduced decorin and biglycan in the peribronchiolar regions from COPD patients with emphysema, compared to those of controls or lung fibrosis patients [40]. The levels of heparan sulphate were reduced in the airway walls of patients with both COPD and lung fibrosis. However, fibronectin was found elevated in the inner / outer layer, and muscle layer of the small airways in COPD patients in contrast to smokers and non-smokers patients, whilst tenascin was increased only in the inner layer of the small airways of COPD compared to controls [38]. Collagen organization also plays an important role in ECM remodeling and the regulation of cellular function. Using second harmonic generation, Tjin and colleagues demonstrated that the organization of type I collagen in the airway wall was significantly different in COPD lung tissue compared with non-disease controls [41]. There are excellent reviews summarizing the changes observed in the lung ECM of COPD subjects [15, 24, 26, 42]. Changes in the expression and organization of ECM molecules in the lung may have an important consequence for the mechanical properties of the lung ECM in the COPD lung. The stiffness of the tissue plays a critical role. Suki and colleagues extensively discussed the importance of collagen and elastin for the mechanical properties of lung parenchyma. Since the stiffness of elastin was demonstrated to be two fold smaller than that of collagen [43], a decrease of elastin may lead to an imbalance in ECM composition and an increase in lung stiffness, which in turn can negatively impact the lung function. Idiopathic Pulmonary Fibrosis (IPF) IPF is a chronic fibrotic lung disease of unknown etiology, characterized by abnormal deposition of ECM in the lung parenchymal regions [44]. While repeated microinjuries to the epithelial layer are thought to be the initiator of an aberrant wound 6
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