A CONTRIBUTION TO THE REGULATION OF PROTEOGLYCAN PRODUCTION - MODULATION BY TGF-ALPHA, TGF-BETA AND IL-1 OF GLYCOSAMINOGLYCAN BIOSYNTHESIS ON BETA-D-XYLOSIDE IN CHICK-EMBRYO FIBROBLASTS

In order to elucidate the mechanisms determining the variability in th e proteoglycan structure and the factors involved in this determinatio n, we treated chick embryo skin fibroblasts with beta-D-xyloside to ob tain glycosaminoglycan chains deprived of core proteins, and with diff erent cytokines (transforming growth factor alpha and beta, interleuki n-1) to produce variability. The different cytokines specifically regu late both cellular and extracellular amount and composition of glycosa minoglycans. beta-D-Xyloside treatment does not change protein content and protein synthesis, whereas it increases overall extracellular sul phated glycosaminoglycan production, heparan sulphate and chondroitin sulphate content, and reduces that of dermatan sulphate. This indicate s that the core protein regulates quantitative proteoglycan production , and probably directs (with appropriate signals) the core oligosaccha ride bound to it to the right synthesizing enzymes. The modulatory act ion of the different cytokines on sulphated glycosaminoglycan producti on and classes remains, even though the core protein is absent. This i ndicates that the cytokines also act on the glycosyltransferases. Our results suggest that the proteoglycan production may be subject to a d ouble control, one of which is at the level of the core protein and th e other, mediated by environmental signals, at the level of glycosamin oglycan synthesizing enzymes.