Bassols A, Massagué J
Department of Biochemistry, University of Massachusetts Medical School, Worcester 01655.
J Biol Chem. 1988 Feb 25;263(6):3039-45.
Transforming growth factor beta (TGF-beta) increases up to 20-fold the expression of various forms of chondroitin/dermatan sulfate proteoglycan, the major type of sulfated proteoglycan present in the extracellular matrix and culture medium of various human, rodent, and mink cell types including kidney and lung fibroblasts, lung epithelial cells, preadipocytes, and skeletal muscle myoblasts. TGF-beta regulates the level and molecular size of these proteoglycans by acting simultaneously at two levels: it elevates the biosynthetic rate of the 45-kDa proteoglycan core protein in a cycloheximide- and actinomycin D-sensitive manner, and it induces an increase in the molecular mass of the glycosaminoglycan chains. These cellular responses correlate with occupancy of type III TGF-beta receptors by TGF-beta 1 and TGF-beta 2 and are not induced by other growth factors tested. The parameters of this effect of TGF-beta in kidney fibroblasts and myoblasts are ED50 = 5-10 pM TGF-beta 1 or TGF-beta 2, and t 1/2 = 6-8 h. These results identify the chondroitin/dermatan sulfate proteoglycans as a major component of mammalian mesenchymal and epithelial extracellular matrices whose expression and structure are regulated by TGF-beta.
转化生长因子β（TGF-β）可使多种形式的硫酸软骨素/硫酸皮肤素蛋白聚糖的表达增加高达20倍，硫酸化蛋白聚糖是包括肾和肺成纤维细胞、肺上皮细胞、前脂肪细胞和骨骼肌成肌细胞在内的各种人类、啮齿动物和貂细胞类型的细胞外基质和培养基中存在的主要硫酸化蛋白聚糖类型。TGF-β通过在两个水平上同时起作用来调节这些蛋白聚糖的水平和分子大小：它以一种对放线菌酮和放线菌素D敏感的方式提高45 kDa蛋白聚糖核心蛋白的生物合成速率，并且它诱导糖胺聚糖链的分子量增加。这些细胞反应与TGF-β1和TGF-β2对III型TGF-β受体的占据相关，并且不会被测试的其他生长因子诱导。TGF-β在肾成纤维细胞和成肌细胞中的这种效应的参数为：ED50 = 5 - 10 pM TGF-β1或TGF-β2，t½ = 6 - 8小时。这些结果表明，硫酸软骨素/硫酸皮肤素蛋白聚糖是哺乳动物间充质和上皮细胞外基质的主要成分，其表达和结构受TGF-β调节。
