权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Studies on the mechanism of actions of a cartilage-derived pleiotrophic growth factor, ecogenin/CTGF - Molecular cloning of its receptors and mechanism of inter- and intra signal transduction -

软骨源性多效生长因子 Ecogenin/CTGF 的作用机制研究 - 其受体的分子克隆以及内部和内部信号转导机制 -

基本信息

批准号：
10470389
负责人：
TAKIGAWA Masaharu
金额：
$ 8.51万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

1) Specific receptors for ecogenin/CTGF were found on chondrocytes, osteoblasts and vascular endothelial cells. Its molecular weight was about 240 kDa.2) Specific binding of radiolabeled ecogenin/CTGF for chondrocytes decreased as the cells differentiated.3) In chondrocyte culture system, ecogenin/CTGF bound cell surface heparan sulfate proteoglycans after secreted and was then released, suggesting that it is a matricrine factor.4) Ecogenin/CTGF stimulated phosphorylation of ERK and p38MAPK in chondrocytes. Using specific inhibitors, we found that ecogenin/CTGF promoted the proliferation and differentiation of chondrocytes through ERK and p38MAPK pathways, respectively.5) Two binding proteins for ecogenin/CTGF were purified from human chondrocytic cell line HCS-2/8. The one was 42 kDa protein of which N-terminal amino acid sequence corresponded to that of γ-actin and the other was 50 kDa protein of which N-terminal amino acid sequence corresponded to that of cytokeratin.6) When ecogenin/CTGF was overexpressed in Cos-7 cells, it localized around centrosome. C-terminal fragment was also found in cells.These findings suggest that ecogenin/CTGF not only acts as a paracrine and matricrine factor through its specfic receptors but also functions through an alternative intracellular pathway.

1)在软骨细胞、成骨细胞和血管内皮细胞上发现了ecogenin/CTGF的特异性受体。2）随着软骨细胞的分化，标记的ecogenin/CTGF与软骨细胞的特异性结合逐渐减弱; 3）在软骨细胞培养体系中，ecogenin/CTGF分泌后与细胞表面硫酸乙酰肝素蛋白多糖结合，然后释放，表明其为一种苦参碱因子; 4）ecogenin/CTGF刺激软骨细胞ERK和p38 MAPK磷酸化。利用特异性抑制剂，我们发现ecogenin/CTGF分别通过ERK和p38 MAPK途径促进软骨细胞的增殖和分化。5）从人软骨细胞系HCS-2/8中纯化了两个ecogenin/CTGF结合蛋白。其中一个为42 kDa蛋白，其N-末端氨基酸序列与γ-actin的序列一致;另一个为50 kDa蛋白，其N-末端氨基酸序列与细胞角蛋白的序列一致。6）ecogenin/CTGF在Cos-7细胞中过表达后，定位于中心体周围。这些结果表明ecogenin/CTGF不仅通过其特异性受体发挥旁分泌和基质分泌因子的作用，而且还通过另一条细胞内途径发挥作用。