UROKINASE-TYPE PLASMINOGEN-ACTIVATOR MEDIATES BASIC FIBROBLAST GROWTH FACTOR-INDUCED BOVINE ENDOTHELIAL-CELL MIGRATION INDEPENDENT OF ITS PROTEOLYTIC ACTIVITY
UROKINASE-TYPE PLASMINOGEN-ACTIVATOR MEDIATES BASIC FIBROBLAST GROWTH FACTOR-INDUCED BOVINE ENDOTHELIAL-CELL MIGRATION INDEPENDENT OF ITS PROTEOLYTIC ACTIVITY
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DOI：
10.1002/jcp.1041500206
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发表时间：
1992-02-01
影响因子：
5.6
通讯作者：
RIFKIN, DB
中科院分区：
文献类型：
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作者：
ODEKON, LE;SATO, Y;RIFKIN, DB
利用损伤内皮细胞单层和基质覆盖技术研究了内皮细胞迁移过程中尿激酶型纤溶酶原激活物（uPA）诱导对内源性碱性成纤维细胞生长因子（bFGF）活性的依赖性。 纯化的多克隆兔免疫球蛋白G（IgG）对碱性成纤维细胞生长因子阻断uPA依赖的裂解活性的外观通常观察到的边缘受伤的牛主动脉内皮（BAE）细胞单层。 此外，bFGF或牛uPA抗体可抑制30-50%的细胞迁移到裸露区域。 用纯化的牛uPA或能够诱导PA活性的试剂（例如佛波醇肉豆蔻酸酯乙酸酯（PMA）、钒酸盐或bFGF）孵育损伤的单层导致细胞的迁移增强（28-50%）。 抗牛uPA IgG阻断了BAE细胞迁移的显着分数（25%）暴露于外源性bFGF诱导。 uPA在损伤BAE细胞迁移中的作用不依赖于纤溶酶的产生。 此外，人重组（hr）uPA的氨基末端片段（ATF），这是酶活性，刺激BAE细胞运动（36%）以及完整的uPA。 ATF的hr uPA也刺激血管内皮细胞运动的存在下，抗bFGF IgG。 这些结果表明，BAE细胞从受伤的单层边缘迁移依赖于内源性bFGF介导的uPA的局部增加。 此外，数据支持的结论是，迁移是通过依赖于uPA受体的占用，但独立于uPA介导的蛋白水解的信号传导机制刺激。
The dependence of urokinase-type plasminogen activator (uPA) induction on endogenous basic fibroblast growth factor (bFGF) activity during endothelial cell migration was investigated utilizing a combination of wounded endothelial cell monolayers and substrate overlay techniques. Purified polyclonal rabbit immunoglobulin G (IgG) against bFGF blocked the appearance of uPA-dependent lytic activity normally observed at the edge of a wounded bovine aortic endothelial (BAE) cell monolayer. Additionally, the migration of cells into the denuded area was inhibited 30-50% by antibodies either to bFGF or to bovine uPA. Incubation of wounded monolayers with either purified bovine uPA or agents able to induce PA activity, such as phorbol myristate acetate (PMA), vanadate, or bFGF, resulted in enhanced migration of cells (28-50%). Anti-bovine uPA IgG blocked a significant fraction (25%) of BAE cell migration induced by exposure to exogenous bFGF. The role of uPA in migration of wounded BAE cells was not dependent on plasmin generation. Furthermore, the amino terminal fragment (ATF) of human recombinant (hr) uPA, which is enzymatically inactive, stimulated BAE cell movement (36%) as well as intact uPA. ATF of hr uPA also stimulated endothelial cell movement in the presence of anti-bFGF IgG. These results suggest that BAE cell migration from the edge of a wounded monolayer is dependent upon local increases of uPA mediated by endogenous bFGF. Moreover, the data support the conclusion that migration is stimulated via a signalling mechanism dependent upon occupancy of the uPA receptor but independent of uPA-mediated proteolysis.