Extracellular matrix remodelling in COPD

Abstract

The extracellular matrix (ECM) of the lung plays several important roles in lung function, as it offers a low resistant pathway that allows the exchange of gases, provides compressive strength and elasticity that supports the fragile alveolar–capillary intersection, controls the binding of cells with growth factors and cell surface receptors and acts as a buffer against retention of water.COPD is a chronic inflammatory respiratory condition, characterised by various conditions that result in progressive airflow limitation. At any stage in the course of the disease, acute exacerbations of COPD may occur and lead to accelerated deterioration of pulmonary function. A key factor of COPD is airway remodelling, which refers to the serious alterations of the ECM affecting airway wall thickness, resistance and elasticity. Various studies have shown that serum biomarkers of ECM turnover are significantly associated with disease severity in patients with COPD and may serve as potential targets to control airway inflammation and remodelling in COPD. Unravelling the complete molecular composition of the ECM in the diseased lungs will help to identify novel biomarkers for disease progression and therapy.

Proteases, Mucus, and Mucosal Immunity in Chronic Lung Disease

“…Extracellular proteases contribute substantially to ECM cleavage and airway remodelling, in both normal and pathological settings, though a thorough investigation of these aspects of protease function is beyond the scope of this review. For further reading, the reader is directed towards the following reviews [ 131 , 133 , 134 ]. Overall, proteases are important effectors of pathogen removal and act as intermediaries in the escalation of appropriate immune responses to pathogenic stimuli in the airways.…”

Emerging role of exosomes in the pathology of chronic obstructive pulmonary diseases; destructive and therapeutic properties

“…Several lines of documents have shown both endothelial cells (ECs) and alveolar epithelial cells displayed apoptotic changes, indicated with enhanced P53 and Caspase activity, after the onset of COPD [ 65 , 66 ]. Histological examinations have indicated that pulmonary ECM like basement membranes and the interstitial matrix is degraded, leading to the lack of suitable elasticity and mechanical stability [ 67 ]. The progressive turnover in the ECM components supports prominent structural modifications and pathological remodeling [ 68 ].…”

“…Due to the airflow obstruction or narrowing, both emphysematous (excessive alveolar dilation) and atelectatic foci are detectable in gross and microscopic examinations [ 88 ]. The increased recruitment of immune cells, neutrophils, eosinophils, and further activation of alveolar macrophages coincides with the release of MMPs and lung destruction and ECM remodeling [ 67 ]. Within the lung parenchyma, the exposure of furnishing epithelial cells to pro-inflammatory cytokines leads to mitochondrial dysfunction and squamous metaplasia (Fig.…”

Roles of Mesenchymal Cells in the Lung: From Lung Development to Chronic Obstructive Pulmonary Disease

“…It has been shown that in different lung compartments, elastic fibers, elastin, glycosaminoglycans (e.g., hyaluronic acid) and type I collagen decrease drastically, but not fibronectin, tenascin and other collagens. These changes contribute to peri-bronchial fibrosis and progressive emphysema that profoundly impact the respiratory functions ( Figure 5 ) [ 156 , 157 , 158 , 159 , 160 ].…”