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Role of proteoglycans in the cell proliferation and thyroid hormone secretion

蛋白多糖在细胞增殖和甲状腺激素分泌中的作用

基本信息

批准号：
62480259
负责人：
SHISHIBA Yoshimasa
金额：
$ 4.29万
依托单位：
Okinaka Memorial Institute for Medical Research
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1989
项目状态：
已结题

项目摘要

Proteoglyean is a macromolecule consisting of glycosaminoglycan chains covalently linked with core-glycoprotein. It is important as a ground substance in cell-culture system such as chondrocytes or osteogenic cells. The synthesis is influenced by hormone in granulosa cells.However, what kind of roles the proteoglyean does play in thyroid tissue in which particular secretory process is operating remain unanswered. In the present study, we have disclosed followings;1. Proteoglycan production in thyroid cells is closely related to the cell proliferation through cAMP dependent mechanism (Shishiba Y, et al. J Biol Chem 263:1745, 1988).2. Proteoglycan was also produced in thyroid organ culture system. Chondroitin sulfate proteoglyean was secreted into medium in a fashion dependent to the dose of TSH, while heparan sulfste proteoglyean remained in the tissue. From the autoradiography of ^<35>S, the kinetics of ^<35>S grain resembled those of thyroglobulin. It was speculated that proteoglyeans … More were produced in epithelial cells, secreted into follicular space and concentrated. Proteoglyeans may function as a mechanical support for the follicular structure in thyroid tissue, as well as in ovary (Shishiba Y, et al. Progress in Thyroidology 1989, p.259, Korea).3. Apart from thyroid tissue, proteoglycan production in fibroblast culture was enhanced by IgG's of Graves' disease with pretibial myxedema. T_3 excess also favors the,synthesis of proteoglycan. The cause of pretibial myxedema is thus the accumulation of proteoglycan produced by fibroblasts stimulated by IgG's and T_3 excess. Whether the same story can be applied to the pathogenesis of malignant exophthalmos in Graves' disease is under study (Shishiba Y, et al. The Thyroid P-385, 1988).4. Proteoglyeans are the regulator of calcification in osteogenic cell culture. In early phase of culture where calcification was not observed, osteogenic cells produced large chondroitin sulfate proteoglyean, small chondroitin sulfate proteoglycan, haparan sulfate proteoglyean and hyaluronic acids. in the calcification phase of culture, the production of these proteoglycan species was decreased dramatically. 1,25(OH)_2D_3, which enhanced calcification, decreased proteoglyean production and accelerated degradation by increasing proteoglyean binding to the receptor. Thus, proteoglyeans are one of the factors to inhibit calcification by occupying the gap junction of collagen fibers. When the production of proteoglyeans is decreased either by aging or by 1,25(OH)_2D_3, calcification starts in the unoccupied gap junction. Less

蛋白质是由糖胺聚糖链与核糖蛋白共价连接而成的大分子。在软骨细胞或成骨细胞等细胞培养系统中，它是一种重要的基质。这种合成受到颗粒细胞中激素的影响。然而，蛋白水解酶在甲状腺组织中扮演着什么样的角色，这一特定的分泌过程正在进行中，目前还没有答案。在本研究中，我们揭示了以下几点：1.甲状腺细胞蛋白多糖的产生与细胞增殖密切相关(Shishiba Y，et al.生物化学263：1745,1988)在甲状腺器官培养体系中也产生了蛋白多糖。硫酸软骨素蛋白以一种依赖于TSH剂量的方式分泌到培养液中，而肝素硫酸酯蛋白仍留在组织中。从S的放射自显影来看，S颗粒的动力学与甲状腺球蛋白相似。据推测，蛋白质酵母的…更多的是在上皮细胞中产生，分泌到滤泡间隙并浓缩。Proteoglyeans可以作为甲状腺组织和卵巢中滤泡结构的机械支撑(Shishiba Y，et al.《甲状腺生物学进展1989》，第259页，韩国)。除甲状腺组织外，Graves病合并胫前粘液水肿的免疫球蛋白可促进成纤维细胞产生蛋白多糖。T_3过量也有利于蛋白多糖的合成。因此，胫前粘液水肿的原因是成纤维细胞在免疫球蛋白和T_3过量刺激下产生的蛋白多糖的积聚。同样的故事是否可以应用于Graves病的恶性突眼的发病机制正在研究中(Shishiba Y，et al.甲状腺P-385,1988)。变形杆菌是成骨细胞培养中钙化的调节者。在未观察到钙化的培养早期，成骨细胞产生大的硫酸软骨素蛋白多糖、小的硫酸软骨素蛋白多糖、硫酸乙酰肝素蛋白多糖和透明质酸。在培养的钙化阶段，这些蛋白多糖的产量急剧下降。1，25(OH)_2D_3促进钙化，通过增加蛋白凝胶与受体的结合，减少蛋白凝胶的产生，加速降解。因此，蛋白凝胶是通过占据胶原纤维缝隙连接来抑制钙化的因素之一。当蛋白凝胶的产量因老化或1，25(OH)_2D_3而减少时，钙化开始于未被占据的缝隙连接。较少