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 the proteoglycan structure and the factors involved in this determination, we treated chick embryo skin fibroblasts with beta-D-xyloside to obtain glycosaminoglycan chains deprived of core proteins, and with different cytokines (transforming growth factor alpha and beta, interleukin-1) to produce variability. The different cytokines specifically regulate both cellular and extracellular amount and composition of glycosaminoglycans. Beta-D-xyloside treatment does not change protein content and protein synthesis, whereas it increases overall extracellular sulphated glycosaminoglycan production, heparan sulphate and chondroitin sulphate content, and reduces that of dermatan sulphate. This indicates that the core protein regulates quantitative proteoglycan production, and probably directs (with appropriate signals) the core oligosaccharide bound to it to the right synthesizing enzymes. The modulatory action of the different cytokines on sulphated glycosaminoglycan production and classes remains, even though the core protein is absent. This indicates that the cytokines also act on the glycosyltransferases. Our results suggest that the proteoglycan production may be subject to a double control, one of which is at the level of the core protein and the other, mediated by environmental signals, at the level of glycosaminoglycan synthesizing enzymes.
Evangelisti
R
R
Istituto di Istologia ed Embriologia Generale, Università degli Studi di Ferrara, Italy. enr@dns.unife.it
Valeno
V
V
Bosi
G
G
Bodo
M
M
Scalabrini
P
P
Stabellini
G
G
Pezzetti
F
F
Carinci
P
P
D000818:Animals; D002642:Chick Embryo; D017077:Culture Media, Conditioned / Q000737:chemistry; D004357:Drug Synergism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006027:Glycosides / Q000378:metabolism* / Q000502:physiology; D007375:Interleukin-1 / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism; D011509:Proteoglycans / Q000096:biosynthesis*; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D017077:Culture Media, Conditioned; D006025:Glycosaminoglycans; D006027:Glycosides; D007375:Interleukin-1; D011509:Proteoglycans; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; C010807:xylosides; D007930:Leucine