Summary
Human platelet-derived transforming growth factor-beta (TGF-beta) is a cell-type specific promotor of proteoglycan synthesis in human adult arterial cells. Cultured human adult arterial smooth muscle cells synthesized chondroitin sulfate, dermatan sulfate, and heparan sulfate proteoglycans, and the percent composition of these three proteoglycan subclasses varied to some extent from cell strain to cell strain. However, TGF-beta consistently stimulated the synthesis of chondroitin sulfate proteoglycan. Both chondroitin 4- and chondroitin 6-sulfate were stimulated by TGF-beta to the same extent. TGF-beta had no stimulatory effect on either class of [35S]sulfate-labeled proteoglycans which appeared in an approximately 1:1 and 2:1 ratio of heparan sulfate to dermatan sulfate of the medium and cell layers, respectively, of arterial endothelial cells. Human adult arterial endothelial cells synthesized little or no chondroitin sulfate proteoglycan. Pulse-chase labeling revealed that the appearance of smooth muscle cell proteoglycans into the medium over a 36-h period equaled the disappearance of labeled proteoglycans from the cell layer, independent of TGF-beta. Inhibitors of RNA synthesis blocked TGF-beta-stimulated proteoglycan synthesis in the smooth muscle cells. The incorporation of [35S]methionine into chondroitin sulfate proteoglycan core proteins was stimulated by TGF-beta. Taken together, the results presented indicate that TGF-beta stimulates chondroitin sulfate proteoglycan synthesis in human adult arterial smooth muscle cells by promoting the core protein synthesis.
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Adams, C. W. M.; Bayliss, O. B. Acid mucosubstances underlying lipid deposits in aging tendons and atherosclerotic arteries. Atherosclerosis 18:191–195; 1973.
Assoian, R. K.; Komoriya, A.; Meyers, C. A., et al. Transforming growth factor in human platelets. Identification of a major storage site, purification and characterization. J. Biol. Chem. 258:7155–7160; 1983.
Assoian, R. K.; Sporn, M. S. Type beta transforming growth factor in human platelets: release during platelet degranulation and action on vascular smooth muscle cells. J. Cell Biol. 102:1217–1223; 1986.
Bassols, A.; Massague, J. Transforming growth factor beta regulate the expression and structure of extracellular matrix chondroitin/dermatan sulfate proteoglycans. J. Biol. Chem. 263:3039–3045; 1988.
Berenson, G. S.; Radhakrishnamurthy, B.; Srinivasan, S. R., et al. Recent advances in molecular pathology. Carbohydrate protein macromolecules and arterial wall integrity-A role in atherosclerosis. Exp. Mol. Pathol. 41:267–287; 1984.
Burke, J.; Ross, R. Synthesis of connective tissue macromolecules by smooth muscle. In: International review of connective tissue research, vol. 8. New York: Academic Press; 1979:119–157.
Camejo, G. The interaction of lipids and lipoproteins with the intercellular matrix of arterial tissue: its possible role in atherogenesis. Adv. Lipid Res. 19:1–53; 1982.
Camejo, G.; Olofsson, S-O.; Lopez, F., et al. Identification of apo B-100 segments mediating the interaction of low density lipoprotein with arterial proteoglycans. Arteriosclerosis 8:368–377; 1988.
Camejo, G.; Ponce, E.; Lopez, F., et al. Partial structure of the active moiety of a lipoprotein complexing proteoglycan from human aorta. Atherosclerosis 49:241–254; 1983.
Chang, Y.; Yanagishita, M.; Hascall, V. C., et al. Proteoglycans synthesized by smooth muscle cells derived from monkey aorta. J. Biol. Chem. 258:5679–5688; 1983.
Chen, J.-K.; Hoshi, H.; McClure, D. B., et al. Role of lipoproteins in growth of human adult arterial endothelial and smooth muscle cells in low lipoprotein-deficient serum. J. Cell. Physiol. 129:207–214; 1986.
Chen, J.-K.; Hoshi, H.; McKeehan, W. L. Transforming growth factor-beta specifically stimulates synthesis of proteoglycan in human adult arterial smooth muscle cells. Proc. Natl. Acad. Sci. USA 84:5287–5291; 1987.
Childs, C. B.; Proper, J. A.; Tucker, P. F., et al. Serum contains a platelet-derived transforming growth factor. Proc. Natl. Acad. Sci. USA 79:5312–5316; 1982.
Dietrich, C. P.; Dietrich, S. M. C. Electrophoretic behaviour of acidic mucopolysaccharides in diamine buffer. Anna. Biochem. 70:645–647; 1976.
Faggiotto, A.; Ross, R. Studies of hypercholesterolemia in the nonhuman primate. II. Fatty streak conversion to fibrous plaque. Arteriosclerosis 4:341–356; 1984.
Gordon, P. B.; Sussman, I. I.; Hatcher, V. B. Long-term culture of human endothelial cells. In Vitro 19:661–671; 1983.
Habuchi, H.; Kimata, K.; Suzuke, S. Changes in proteoglycan composition during development of rat skin. The occurrence in fetal skin of a chondroitin sulfate proteoglycan with high turnover rate. J. Biol. Chem. 261:1031–1040; 1986.
Hascall, J. R.; Kimura, J. H.; Hassel, V. C. Proteoglycan core protein families. Ann. Rev. Biochem. 55:539–567; 1986.
Hollander, W. Unified concept on the role of acid mucopolysaccharides and connective tissue proteins in the accumulation of lipids. Exp. Mol. Pathol. 25:106–120; 1976.
McKeehan, W. L.; Crabb, J. W. Isolation of multiple chromatographic forms of type one heparin-binding growth factors from bovine brain. Anal. Biochem. 164:563–569; 1987.
McKeehan, W. L.; McKeehan, K. A. Calcium, magnesium and serum factors in multiplication of normal and transformed human lung fibroblasts. In Vitro 16:475–485; 1980.
Mozzicato, P.; Faris, B.; Hollander, W., et al. A method to evaluate the biosynthesis of glycosaminoglycans by the aorta of Cynomolgus monkey. Atherosclerosis 45:359–363; 1982.
Mourao, P. A. S.; Luz, M. R. M. P.; Borojevic, R. Sulfated proteoglycans synthesized by human smooth muscle cells isolated from different organs. Biochim. Biophys. Acta 881:321–329; 1986.
Oegema, T. R., Jr.; Hascall, V. C.; Eisenstein, R. Characterization of bovine aorta proteoglycan extracted with guanidine hydrochloride in the presence of protease inhibitors. J. Biol. Chem. 254:1312–1318; 1979.
Radhakrishnamurthy, B.; Srinivasan, S. R.; Vijayagopal, P., et al. In: Varma, R. S.; Varma, R., eds. Glycosaminoglycans and proteoglycans in pathological processes. Basal: Karger; 1982:231–251.
Ross, R. Atherosclerosis—a problem of the biology of arterial wall cells and their interactions with blood components. Arteriosclerosis 1:293–331; 1981.
Ross, R.; Glomset, J. A. Atherosclerosis and the arterial smooth muscle cells: proliferation of smooth muscle is a key event in the genesis of the lesions of atherosclerosis. Science 180:1332–1339; 1973.
Salisburry, B. G. J.; Falcone, D. J.; Minick, C. R. Insoluble lipoprotein-proteolgycan complexes enhance cholesteryl ester accumulation in macrophages. Am. J. pathol. 120:6–11; 1985.
Salisburry, B. G. J.; Wagner, W. D. Isolation and preliminary characterization of proteoglycans dissociatively extracted from human aorta. J. Biol. Chem. 256:8050–8057; 1981.
Srinivasan, S. R.; Dolan, P.; Radhakrishnamurthy, B., et al. Isolation of lipoprotein-acid mucopolysaccharide complexes from fatty streaks of human aortas. Atherosclerosis 16:95–104; 1972a.
Srinivasan, S. R.; Dolan, P.; Radhakrishnamurthy, B., et al. Isolation of lipoprotein-acid mucopolysaccharide complexes from fatty streaks of human aortas. Prep. Biochem. 2:83–91; 1972b.
Srinivasan, S. R.; Yost, K.; Radhakrishnamurthy, B., et al. Lipoprotein-hyaluronate association in human aorta fibrous plaque lesions. Atherosclerosis 36:25–37; 1980.
Steele, R. H.; Wagner, W. D.; Rowe, H. A., et al. Artery wall derived proteoglycan-plasma lipoprotein interaction: lipoprotein binding properties of extracted proteoglycans. Atherosclerosis 65:51–62; 1987.
Vijayagopal, P.; Srinivasan, S. R.; Radhakrishnamurthy, B., et al. Interactions of serum lipoproteins and a proteoglycan from bovine aorta. J. Biol. Chem. 256:8234–8241; 1981.
Wagner, W. D.; Rowe, H. A.; Conner, J. R. Biochemical characteristics of dissociatively isolated aortic proteoglycans and their binding capacity to hyaluronic acid. J. Biol. Chem. 258:11136–11142; 1983.
Walton, K. W.; Williamson, N. Histological and immunofluorescent studies in the evolution of the human atheromatous plaque. J. Atheroscler. Res. 8:599–624; 1968.
Wight, T. N. Vessel proteoglycans and thrombosis. In: Spaet, T. H., ed. Progress in hemostasis and thrombosis. New York: Grune and Stratton 5:1–39; 1980.
Wight, T. N.; Lark, M. W.; Kinsella, M. G. Blood vessel proteoglycans. In: Wight, T. N.; Mecham, R. P., eds. Biology of extracellular matrix: biology of proteoglycans. Orlando, FL: Academic Press; 1987:267–300.
Wight, T. N. Proteoglycans in pathological conditions: atherosclerosis. Fed. Proc. 44:381–385; 1985.
Wight, T. N. Cell biology of arterial proteoglycans. Arteriosclerosis 9:1–20; 1989.
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Supported in part by grants from the Public Health Service, U.S. Department of Health and Human Services, Washington, DC (CA 37589 and HL 33842), RJR Nabisco, Inc., and Chang Gung Biomedical Research Foundation (CMRP 291).
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Chen, JK., Hoshi, H. & McKeehan, W.L. Stimulation of human arterial smooth muscle cell chondroitin sulfate proteoglycan synthesis by transforming growth factor-beta. In Vitro Cell Dev Biol - Animal 27, 6–12 (1991). https://doi.org/10.1007/BF02630888
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DOI: https://doi.org/10.1007/BF02630888