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.

在低氧条件下，培养的血管内皮细胞对胶原蛋白XVIII基因的表达显着降低。当通过特定的单克隆抗体分析时，还降低了胶原蛋白XVIII蛋白水平。Endostatin诱导体内软骨肉瘤生长和肿瘤血管生成的消退。然而，内接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，我们详细研究了内骨和内皮细胞之间的相互作用。内抑素抑制了胶原蛋白I的迁移和附着，但不影响内皮细胞的增殖。尽管内皮细胞的迁移被诸如基本成纤维细胞生长因子和血管内皮生长因子之类的血管生成因子刺激，但在存在或不存在兴奋剂的情况下，内抑素对其表现出相似的抑制作用。即，上皮下基底膜通常包含XVIII型，而骨骼和心肌则具有突出的XV型。但是，血管组织中平滑肌细胞周围的地下膜含有一个或两者，具体取决于其位置。有趣的是，连续或体细胞毛细血管在其地下膜中含有XV型和XVIII型胶原蛋白。然而，诸如肾小球，肝正弦，肺肺单抗和脾辛西拉丝等毛细血管的毛细血管中仅在其地下膜上仅表达XVIII型链，缺乏XV型链条。该观察结果可能意味着在各种组织和器官中使用不同机制来控制血管生成的各种组织和器官中的不同功能。