Extracellular matrix in connective tissue

Kielty, C.M., Hopkinson, 1., Grant, M.E. Collagen structure, assembly and organization in the extracellular matrix. In Connective Tissue and its Heritable Disorders Wiley-Liss, Chichester, pp. 103-147, 1993. 

In contrast, some cytokines (e.g. some CSFs and EPO) appear to be expressed constitutively. In yet other instances cytokines such as PDGF and TGF-P are stored in cytoplasmic granules and can be rapidly released in response to appropriate stimuli. Other cytokines (mainly ones with growth factor activity, e.g. TGF-P, FGF and IL-1) are found bound to the extracellular matrix in connective tissue, bone and skin. These are released, bringing about a biological response upon tissue injury. 

Kielty, C. M., and Grant, M. E. (2002). The Collagen Family Structure Assembly and Organization in the Extracellular Matrix. In Connective Tissue and its Heritable Disorders, (P. M. Royce andB. Steinmann, Eds.), pp. 159-222. Wiley-Liss, New York. 

Proteoglycans Glycosaminoglycans (mucopolysaccharides) bound to protein chains in covalent complexes. Proteoglycans are present in the extracellular matrix of connective tissue. 

Proteoglycan aggregates are typically found in the extracellular matrix of connective tissue. The noncovalent attachment of each proteoglycan to hyaluronic acid via the core protein is mediated by two linker proteins (not shown). Proteoglycans interact with numerous fibrous proteins in the extracellular matrix such as collagen, elastin, and fibronectin (a glycoprotein involved in cell adhesion). 

Fibrillar Collagens Are the Major Fibrous Proteins in the Extracellular Matrix of Connective Tissues... 

The matrix formed in the presence of carbohydrates may be compared with the extracellular matrix of connective tissues. However, the plaque polysaccharides are not glycosaminoglycans but glucans and other high molecular weight homo- and hetero-polysaccharides which are interspersed with the protein component. Examination of the extracellular polysaccharides... 

Cleary, E. G. (1987). The microfibrillar component of the elastic fibers. In Connective Tissue Disease. Molecular Pathology of the Extracellular Matrix (J. Uitto and A. J. Perejda, Eds.), pp. 55-81. Dekker, New York. 

During inflammation, degranulation of immune cells releases serine proteases that pass through and bind to the capillary wall. Increased levels of Bik suppress these immune cell proteases and protect the extracellular matrix in arterial walls and connective tissue [4]. Bik inhibits phagocytic destruction of cells. Bik has been shown to inhibit elastases, granzymes A and K [4, 57], Mast cell tryptases (J3- and a-tetrameric forms with a molecular weight of 134 kDa) are resistant to aprotinin [58]. Lymphocytes serine esterase TL2 is not inhibited by Bik [59]. 

Collagen is the major insoluble fibrous protein in the extracellular matrix and in connective tissue 80-90% of the collagen in the body consists of types 1, It and 111 (Table 12.2). The collagen superfamily consists of at least 20 collagen types, with as many as 38 distinct polypeptide chains and more than 15 additional proteins that have collagen-like domains. 

Proteoglycans resemble polysaccharides more than proteins in as much as the carbohydrate makes up as much as 95% of the hiomolecule hy weight. Proteoglycans function as lubricants and structural components in connective tissue, mediate adhesion of cells to the extracellular matrix, and bind factors that stimulate cell proliferation. 

Hyaluronan is continuously synthesized and secreted by fibroblasts, keratino-cytes, chondrocytes and other specialized cells in the extracellular matrix (ECMs) throughout the body. It is synthesized by HA synthase (see also Chapter 9) at the inner face of the plasma membrane [98]. The level of HA synthesis is very high in skin and cartilage [99]. Hyaluronic acid is not one of the major components of the ECMs of the connective tissues, but it is found in various locations such as synovial fluid, vitreous humor, and umbilical cords [100]. Its biological functions include the maintenance of mechanical properties such as swelling in connective tissues and control of tissue hydration, providing lubricating properties in synovial fluid and heart valves. 

Connective tissue, such as tendon and cartilage, differs from other solid tissues In that most of Its volume Is made up of extracellular matrix rather than cells. This matrix Is packed with Insoluble protein fibers and contains proteoglycans, various multladhesive proteins, and hyaluronan, a very large, nonsulfated GAG. The most abundant fibrous protein In connective tissue Is collagen. Rubberlike elastin fibers, which can be stretched and relaxed, also are present In deformable sites (e.g., skin, tendons, heart). As discussed later, the fibronectins, a family of multladhesive matrix proteins, form their own distinct fibrils In the matrix of some connective tissues. Although several types of cells are found In connective tissues, the various ECM components are produced largely by cells called fibroblasts. 

Many of the cells in tissues are embedded in an extracellular matrix that fills the spaces between cells and binds cells and tissue together. In so doing, the extracellular matrix aids in determining the shape of tissues as well as the nature of the partitioning between tissue types. In the skin, loose connective tissue beneath epithelial cell layers consists of an extracellular matrix in which fibroblasts, blood vessels, and other components are distributed (Fig 49.1). Other types of connective tissue, such as tendon and cartilage, consist largely of extracellular matrix, which is principally responsible for their structure and function. This matrix also forms the sheetlike basal laminae, or basement membranes, on which layers of epithelial cells rest, and which act as supportive tissue for muscle cells, adipose cells, and peripheral nerves. 

Fig. 49.1. An overview of connective tissue extracellular matrix. Supporting the epithelial cell layer is a basal lamina, beneath which are collagen, elastic fibers, and proteoglycans. The cell types present in connective tissue, such as fibroblasts and macrophages, have been removed from the diagram for clarity.

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