小型GTP结合蛋白Rac是血管内皮生长因子诱导的内皮化和血管透性的重要媒介
Anna Eriksson1, Renhai Cao, Joy Roy
1Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
Circulation
|March 26, 2003
概括
血管内皮生长因子 (VEGF) 通过Rac激活引起血管泄漏. 拉斯抗剂阻断了这种泄漏,对血管生长的影响最小,这表明了治疗潜力.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 已知血管内皮生长因子 (VEGF) 诱导血管生成和血管透性.
- 控制VEGF诱导的血管透性的精确信号通路尚未完全理解.
研究的目的:
- 阐明VEGF诱导的血管透性背后的信号机制.
- 研究小GTP结合蛋白Rac在VEGF信号传递中的作用.
主要方法:
- 鼠标角膜微袋试验,迈尔斯试验,细胞化学,电子显微镜和生物化学试验.
- 使用了一种细胞透的Rac抗剂 (TAT-RacN17).
- 内皮细胞培养研究检查受体酸化和下游信号通路.
主要成果:
- 与FGF-2不同的是,VEGF诱导了带有的内皮的毛细血管,与增加的透性相关.
- 拉斯抗剂 (TAT-RacN17) 抑制了VEGF诱导的血管泄漏和化形成,但只部分影响了血管生成.
- 通过VEGFR-2酸化,VEGF信号激活Rac,PLCgamma,Akt,eNOS和Erk1/2;PI3K在Rac和Akt-eNOS的上游作用.
结论:
- 小型GTP结合蛋白Rac对于调解VEGF诱导的血管透性至关重要,在新血管化中起的作用较小.
- 在缺血病条件下,rac对抗剂显示出治疗或预防VEGF介导的血管泄漏和的潜力.
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