Transforming growth factor beta regulates the expression and structure of extracellular matrix chondroitin/dermatan sulfate proteoglycans.
Transforming growth factor beta regulates the expression and structure of extracellular matrix chondroitin/dermatan sulfate proteoglycans.
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DOI：
10.1016/s0021-9258(18)69173-2
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发表时间：
1988-02
期刊：
影响因子：
--
通讯作者：
A. Bassols;J. Massagué
中科院分区：
文献类型：
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作者：
A. Bassols;J. Massagué
转化生长因子β（TGF-β）使各种形式的软骨素/硫酸皮肤素蛋白聚糖的表达增加高达20倍，软骨素/硫酸皮肤素蛋白聚糖是存在于各种人、啮齿动物和貂细胞类型（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）的细胞外基质和培养基中的主要类型的硫酸化蛋白聚糖。TGF-β通过在两个水平同时起作用来调节这些蛋白聚糖的水平和分子大小：它以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-β 1和TGF-β 2对III型TGF-β受体的占用相关，并且不受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作用的参数是ED 50 = 5-10 pM TGF-β 1或TGF-β 2，并且t1/2 = 6-8 h。这些结果鉴定了软骨素/硫酸皮肤素蛋白聚糖作为哺乳动物间充质和上皮细胞外基质的主要组分，其表达和结构受TGF-β调节。
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.