Stimulation of human arterial smooth muscle cell chondroitin sulfate proteoglycan synthesis by transforming growth factor-beta.
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. Pulsechase 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.
Chen
J K
JK
Department of Physiology, Chang Gung Medical College, Taoyuan, Taiwan, R.O.C.
Hoshi
H
H
McKeehan
W L
WL
D000328:Adult; D000546:Amanitins / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis* / Q000302:isolation & purification; D003609:Dactinomycin / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000096:biosynthesis* / Q000302:isolation & purification; D006801:Humans; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011509:Proteoglycans / Q000302:isolation & purification; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000546:Amanitins; D011508:Chondroitin Sulfate Proteoglycans; D006025:Glycosaminoglycans; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D003609:Dactinomycin