Inhibitory mechanism of vascular endothelial cell proliferation by endostatin

内皮抑素抑制血管内皮细胞增殖的机制

基本信息

批准号：
11470274
负责人：
NINOMIYA Yoshifumi
金额：
$ 8.9万
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：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470274/
关键词：
endostatin type XVIII collagen vascular endothelial cells type XV collagen basement membrane

项目摘要

Under low oxygen condition, expression of collagen XVIII gene by cultured vascular endothelial cells reduced significantly. When it was analyzed by specific monoclonal antibodies, the collagen XVIII protein level was also reduced.Endostatin induced regression of chondrosarcoma growth and tumor angiogenesis in vivo. However, endostatin showed no effects on the proliferation and migration of chondrosarcoma cells in vitro. Next, we investigated the interactions between endostatin and endothelial cells in detail. Endostatin inhibited the migration and attachment on collagen I but did not affect proliferation of endothelial cells. Although the migration of endothelial cells was stimulated with angiogenic factors such as basic fibroblast growth factor and vascular endothelial growth factor, endostatin showed similar inhibitory effects on it in the presence or absence of stimulants.We came to the conclusion that non-vascular BMs contain predominantly one of the two types; I.e., subepithelial basement membranes contained type XVIII in general, whereas skeletal and cardiac muscles harbored prominently type XV. But basement membranes surrounding smooth muscle cells in vascular tissues contained one or both of them, depending on their locations. Interestingly, continuous or somatic capillaries contained both type XV and type XVIII collagens in their basement membranes; however, fenestrated or specialized capillaries such as glomeruli, liver sinusoids, lung alveoli, and splenic sinusoids expressed only type XVIII chains in their basement membranes, lacking type XV chain. This observation could imply different functions of basement membranes in various tissues and organs that use different mechanisms for the endogenous control of angiogenesis.

低氧条件下，培养的血管内皮细胞XVIII胶原蛋白基因的表达显着降低。当用特异性单克隆抗体分析时，XVIII 胶原蛋白水平也降低。内皮抑素诱导体内软骨肉瘤生长和肿瘤血管生成的消退。然而，内皮抑素在体外对软骨肉瘤细胞的增殖和迁移没有影响。接下来，我们详细研究了内皮抑素和内皮细胞之间的相互作用。内皮抑素抑制 I 型胶原蛋白的迁移和附着，但不影响内皮细胞的增殖。尽管碱性成纤维细胞生长因子和血管内皮生长因子等血管生成因子刺激内皮细胞的迁移，但在存在或不存在刺激物的情况下，内皮抑素对其表现出相似的抑制作用。我们得出的结论是，非血管BM主要含有两种类型之一；即，上皮下基底膜通常含有 XVIII 型，而骨骼肌和心肌则主要含有 XV 型。但血管组织中平滑肌细胞周围的基底膜含有其中一种或两种，具体取决于它们的位置。有趣的是，连续毛细血管或体细胞毛细血管的基底膜中同时含有 XV 型和 XVIII 型胶原蛋白；然而，有窗或特殊的毛细血管，如肾小球、肝窦、肺泡和脾窦，在其基底膜中仅表达 XVIII 型链，缺乏 XV 型链。这一观察结果可能意味着不同组织和器官中基底膜的不同功能，使用不同的机制来内源性控制血管生成。