Abstract
The extracellular matrix (ECM) plays a significant role in the mechanical behaviour of the lung parenchyma. The ECM is composed of a three-dimensional fibre mesh that is filled with various macromolecules, among which are the glycosaminoglycans (GAGs). GAGs are long, linear and highly charged heterogeneous polysaccharides that are composed of a variable number of repeating disaccharide units. There are two main types of GAGs: nonsulphated GAG (hyaluronic acid) and sulphated GAGs (heparan sulphate and heparin, chondroitin sulphate, dermatan sulphate, and keratan sulphate). With the exception of hyaluronic acid, GAGs are usually covalently attached to a protein core, forming an overall structure that is referred to as proteoglycan. In the lungs, GAGs are distributed in the interstitium, in the sub-epithelial tissue and bronchial walls, and in airway secretions. GAGs have important functions in lung ECM: they regulate hydration and water homeostasis; they maintain structure and function; they modulate the inflammatory response; and they influence tissue repair and remodelling. Given the great diversity of GAG structures and the evidence that GAGs may have a protective effect against injury in various respiratory diseases, an understanding of changes in GAG expression that occur in disease may lead to opportunities to develop innovative and selective therapies in the future.
Highlights
The extracellular matrix (ECM) is composed of a three-dimensional fibre mesh that is filled with various macromolecules, among which are the glycosaminoglycans (GAGs)
Given the great diversity of GAG structures and the evidence that GAGs may have a protective effect against injury in various respiratory diseases, an understanding of changes in GAG expression that occur in disease may lead to opportunities to develop innovative and selective therapies in the future
The alveolar wall is composed of an epithelial cell layer and its basement membrane, the capillary basement membrane and endothelial cells, and a thin layer of interstitial space lying between the capillary endothelium and the alveolar epithelium, which is the extracellular matrix (ECM) [1]
Summary
The alveolar wall is composed of an epithelial cell layer and its basement membrane, the capillary basement membrane and endothelial cells, and a thin layer of interstitial space lying between the capillary endothelium and the alveolar epithelium, which is the extracellular matrix (ECM) [1]. These findings indicate that the function of PGs and GAGs in the lung is not limited to maintenance of mechanical and fluid dynamic properties of the organ These molecules play roles in tissue development and recovery after injury, interacting with inflammatory cells, proteases and growth factors. Some chemokines are released as high-molecularweight complexes associated with proteoglycans, and heparin and heparan sulphate can inhibit chemokine function; these findings suggest that some GAG interactions can prevent inappropriate chemokine activation. On the observation that synthesis of hyaluronic acid is a very early response to connective tissue cell activation in vitro, a rather attractive hypothesis is that inflammation and tissue repair (processes that involve migration and proliferation of cells and that require a vast array of paracrine mechanisms) require an environment with a water concentration considerably higher than that of many mature organs. That human emphysema is a complex disease in which elastic fibre degradation may be one of many factors that cause alveolar destruction [5]
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