A Fibrillar collagen and elastin B Proteoglycan C bFGF regulation by association with the extracellular matrix
Fig. 1.15 ECM components. (A) Fibrillar collagen, and elastic tissue structures. Because of rodlike fibril stacking and extensive lateral crosslinking, collagen fibers have marked tensile strength but little elasticity. Elastin also is crosslinked but differs in having large hydrophobic segments that form a dense globular configuration at rest. As stretch is exerted, the hydrophobic domains are pulled open, but the crosslinks keep the molecules intact; release of the tension allows the hydrophobic domains of the proteins to refold. (B) Proteoglycan structure. The highly negatively charged sulfated sugars on the proteoglycan “bristles” attract sodium and water to generate a viscous compressible matrix. (C) Regulation of basic FGF (bFGF, FGF-2) activity by ECM and cellular proteoglycans. Heparan sulfate binds bFGF secreted in the ECM. Syndecan is a cell surface proteoglycan with a transmembrane core protein and extracellular glycosaminoglycan side chains that bind bFGF, and a cytoplasmic tail that interacts with the intracellular actin cytoskeleton. Syndecan side chains bind bFGF released from damaged ECM, thus facilitating bFGF interaction with cell surface receptors.
post-translational modification that requires hydroxylation of lysine residues in collagen by the enzyme lysyl oxidase. Because lysyl oxidase is a vitamin C-dependent enzyme, children with ascorbate deficiency have skeletal deformities, and people of any age with vitamin C deficiency heal poorly and bleed easily because of “weak” collagen. Genetic defects in collagens cause diseases such as osteogenesis imperfecta and certain forms of Ehlers-Danlos syndrome (Chapter 7).
• Nonfibrillar collagens variously contribute to the structures of planar basement membranes (type IV collagen); help regulate collagen fibril diameters or collagen-collagen interactions via so-called “fibril-associated collagen with interrupted triple helices” (FACITs, such as type IX collagen in cartilage); and provide anchoring fibrils within basement membrane beneath stratified squamous epithelium (type VII collagen).
Elastin. The ability of tissues to recoil and recover their shape after physical deformation is conferred by elastin (
Fig. 1.15 ). Elasticity is especially important in cardiac valves and large blood vessels, which must accommodate recurrent pulsatile flow, as well as in the uterus, skin, and ligaments. Morphologically, elastic fibers consist of a central core of elastin with an associated meshlike network composed of fibrillin. The latter relationship partially explains why fibrillin defects lead to skeletal abnormalities and weakened aortic walls, as in individuals with Marfan syndrome. Fibrillin also controls the availability of TGF-β (Chapter 7).