矩阵金属蛋白酶通过作为细胞周纤维蛋白酶来调节新血管化
1Department of Internal Medicine and University of Michigan Comprehensive Cancer Center, Ann Arbor 48109, USA.
Cell
|November 14, 1998
概括
内皮细胞使用矩阵金属蛋白酶 (MMP),而不是等离子素激活剂,在新血管形成 (血管生成) 过程中分解纤维素屏障. 膜绑定的MMP是这个过程的关键.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 生理学 生理学 生理学
背景情况:
- 血管新生涉及通过纤维素矩阵的内皮细胞入侵.
- 驱动这种入侵的蛋白质分解机制以前是未定义的.
- 在这个过程中,等离子体激活剂 (PA) -等离子体系统的作用尚不清楚.
研究的目的:
- 阐明内皮细胞在血管生成过程中穿透纤维素屏障时使用的蛋白质分解机制.
- 确定PA-plasminogen系统与矩阵金属蛋白酶 (MMPs) 在这个过程中的作用.
主要方法:
- 使用了缺乏PA和等离子素的小鼠组织.
- 在体外和体内评估纤维素凝的新血管化.
- 使用内皮细胞的基因转移与矩阵金属蛋白酶,包括膜类型-1 MMP (MT1-MMP).
主要成果:
- 新血管化有效地发生在缺乏PA或等离子素的组织中,这表明这些系统不需要.
- 内皮细胞衍生的MMPs在血管生成过程中对于纤维素屏障透至关重要.
- 与膜结合的MT1-MMP转移恢复了以前无能细胞的入侵.
- 一个被删除的,但活跃的,MT1-MMP突变体未能恢复入侵,突出显示了膜局部化的重要性.
结论:
- 确定了一种新型的,不依赖PA的纤维解质通路,对血管生成至关重要.
- 证明了与膜结合的MMPs,特别是MT1-MMP,充当细胞周纤维素.
- 确立了MMPs作为通过纤维素在新血管化过程中侵入内皮细胞的关键调节剂.
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