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The extracellular matrix (ECM) is a complex network of different components, responsible for determining and maintaining tissue architecture, and for mediating a number of important biological events. It is composed of a large number of diverse protein families, each constituted by many different individual members. These include the collagens, encoded by 42 different genes, elastin and associated microfibrillar proteins, fibronectin, proteoglycans, and many more molecules. (See Table 63-1.)
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Although all of these proteins are genetically, structurally, and biologically diverse, a common denominator is that most of them have a modular structure, and they are composed of one, a few, or several copies of a limited set of individual structural modules, also called domains.1 These can be combined in multiple ways giving rise to proteins as diverse as fibrillin and laminin (Fig. 63-1). Specific functions have been unraveled for some of these domains, for instance, interaction with other ECM proteins, cell adhesion-promoting activity, cytokine trapping, and regulation. Therefore, the ECM has a critical role for many cellular functions, including proliferation, survival, polarity, differentiation, expression of specific genes, and migration.2–4 All different cell types, such as mesenchymal, epithelial, and endothelial cells, and also inflammatory and tumor cells, participate in the production of distinct ECM macromolecules, and are all influenced by interactions with these compounds. It is well established that the ECM determines the biophysical properties of connective tissues. More recently it became clear that, conversely, stiffness and compliance of connective tissues are important factors for the regulation of cellular functions.5–8
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