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  • Title: Proteoglycans and Diseases of Soft Tissues.
    Author: Hwang CT, Halper J.
    Journal: Adv Exp Med Biol; 2021; 1348():127-138. PubMed ID: 34807417.
    Abstract:
    Proteoglycans consist of protein cores to which at least one glycosaminoglycan chain is attached. They play important roles in the physiology and biomechanical function of tendons, ligaments, cardiovascular system, and other systems through their involvement in regulation of assembly and maintenance of extracellular matrix, and through their participation in cell proliferation together with growth factors. They can be divided into two main groups, small and large proteoglycans. The small proteoglycans are also known as small leucine-rich proteoglycans (SLRPs) which are encoded by 18 genes and are further subclassified into Classes I-V. Several members of Class I and II, such as decorin and biglycan from Class I, and Class II fibromodulin and lumican, are known to regulate collagen fibrillogenesis. Decorin limits the diameter of collagen fibrils during fibrillogenesis. The function of biglycan in fibrillogenesis is similar to that of decorin. Though biomechanical function of tendon is compromised in decorin-deficient mice, decorin can substitute for lack of biglycan in biglycan-deficient mice. New data also indicate an important role for biglycan in disorders of the cardiovascular system, including aortic valve stenosis and aortic dissection. Two members of the Class II of SLRPs, fibromodulin and lumican bind to the same site within the collagen molecule and can substitute for each other in fibromodulin- or lumican-deficient mice.Aggrecan and versican are the major representatives of the large proteoglycans. Though they are mainly found in the cartilage where they provide resilience and toughness, they are present also in tensile portions of tendons and, in slightly different biochemical form in fibrocartilage. Degradation by aggrecanase is responsible for the appearance of different forms of aggrecan and versican in different parts of the tendon where these cleaved forms play different roles. In addition, they are important components of the ventricularis of cardiac valves. Mutations in the gene for versican or in the gene for elastin (which binds to versican ) lead to severe disruptions of normal developmental of the heart at least in mice.
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