Endocan is a novel chondroitin sulfate/dermatan sulfate proteoglycan that promotes hepatocyte growth factor/scatter factor mitogenic activity
Endocan is a novel chondroitin sulfate/dermatan sulfate proteoglycan that promotes hepatocyte growth factor/scatter factor mitogenic activity
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DOI：
10.1074/jbc.m108395200
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发表时间：
2001-12-21
影响因子：
4.8
通讯作者：
Lassalle, P
中科院分区：
文献类型：
--
作者：
Béchard, D;Gentina, T;Lassalle, P
蛋白聚糖可以调节生长因子、趋化因子和凝血因子的活性，进而调节血管内皮的炎症、止血和血管生成等过程。内皮细胞特异性分子-1 （Endothelial cell-specific molecule-1）主要由内皮细胞表达，并受促炎细胞因子的调控（Lassalle， P., Molet， S., Janin， A., Heyden， J. V., Tavernier， J., Fiers， W., Devos， R., Tonnel， A. B., 1996）。化学，271,20458-20464)。我们证明这个分子是作为可溶性皮肤聚糖硫酸盐（DS）蛋白聚糖分泌的。这种蛋白多糖代表了细胞系分泌或在人体血液中循环的主要形式。由于这种蛋白多糖是由内皮细胞特异性分泌的，我们建议将其命名为内啡肽。内聚糖的糖胺聚糖组分由一条与丝氨酸137共价连接的DS链组成。内啡肽剂量依赖性地增加了肝细胞生长因子/分散因子（HGF/SF）介导的人胚胎肾细胞的增殖，而内啡肽的非糖化形式则没有。此外，从内源性纯化的DS链模拟了内源性介导的HGF/SF存在下细胞增殖的增加。总之，我们的研究结果表明，内啡肽是一种由内皮细胞产生的新型可溶性皮肤硫酸酯蛋白多糖。内啡肽调节HGF/SF介导的有丝分裂活性，可能不仅支持HGF/SF在胚胎发生和损伤后组织修复中的功能，还支持肿瘤进展。
Proteoglycans that modulate the activities of growth factors, chemokines, and coagulation factors regulate in turn the vascular endothelium with respect to processes such as inflammation, hemostasis, and angiogenesis. Endothelial cell-specific molecule-1 is mainly expressed by endothelial cells and regulated by pro-inflammatory cytokines (Lassalle, P., Molet, S., Janin, A., Heyden, J. V., Tavernier, J., Fiers, W., Devos, R., and Tonnel, A. B. (1996) J. Biol. Chem. 271, 20458-20464). We demonstrate that this molecule is secreted as a soluble dermatan sulfate (DS) proteoglycan. This proteoglycan represents the major form either secreted by cell lines or circulating in the human bloodstream. Because this proteoglycan is specifically secreted by endothelial cells, we propose to nam it endocan. The glycosaminoglycan component of endocan consists of a single DS chain covalently attached to serine 137. Endocan dose-dependently increased the hepatocyte growth factor/scatter factor (HGF/SF)-mediated proliferation of human embryonic kidney cells, whereas the nonglycanated form of endocan did not. Moreover, DS chains purified from endocan mimicked the endocan-mediated increase of cell proliferation in the presence of HGF/SF. Overall, our results demonstrate that endocan is a novel soluble dermatan sulfate proteoglycan produced by endothelial cells. Endocan regulates HGF/SF-mediated mitogenic activity and may support the function of HGF/SF not only in embryogenesis and tissue repair after injury but also in tumor progression.