科尔塔克丁与VE-cadherin构成复合体,通过Rap1/Rac1激活,对于内皮附着体结节稳定性是必需的
Sina Moztarzadeh1, Sara Sepic1, Ibrahim Hamad1
1Chair of Vegetative Anatomy, Faculty of Medicine, Ludwig-Maximilians-University (LMU) Munich, Pettenkoferstraße 11, 80336, Munich, Germany.
Scientific reports
|January 12, 2024
概括
皮质素 (Cttn) 对于维护血管屏障完整性至关重要,它通过确保适当的结节蛋白分布和支持cAMP介导的信号通路来维持血管屏障完整性. 它的缺失损害了内皮屏障的功能,并影响了恢复.
科学领域:
- 内皮细胞生物学 内皮细胞生物学
- 蜂信号传输是如何进行的
- 血管的通透性 血管的通透性
背景情况:
- 血管透性由皮质素 (Cttn),循环腺氨酸单酸盐 (cAMP),Rho GTPases以及动蛋白细胞骨架进行调节.
- 在关节蛋白相互作用和影响细胞间接触的信号通路中Cttn的确切作用尚不清楚.
研究的目的:
- 为了研究Cttn与结节元件的直接相互作用.
- 阐明Cttn在调节内皮壁功能和细胞骨动态的信号通路中的作用.
主要方法:
- 利用了来自野生类型和Cttn-knock-out小鼠的不朽化微血管心肌内皮细胞.
- 进行了免疫沉,以确定Cttn与VE-cadherin的关联.
- 在补充和cAMP刺激 (福斯科林/罗利普拉姆) 后评估了内皮屏障完整性和恢复.
- 分析了Rap1和Rac1信号通路的激活.
主要成果:
- 缺少Cttn导致屏障完整性受到损害,并导致结节蛋白的分散分布.
- 发现Cttn是基于VE-cadherin的附着结合复合体的一部分.
- 缺少Cttn损害了补充后的屏障恢复和破坏了Rap1/Rac1激活.
- 尽管没有Cttn,但直接激活Rho GTPases增加了屏障抵抗.
结论:
- 皮质素对于通过适当的结节蛋白位址来维持基底内皮质屏障完整性至关重要.
- 通过Rap1/Rac1信号通路,Cttn在cAMP介导的内皮屏障调节中发挥着关键作用.
- 这些发现强调了Cttn作为血管透性和内皮细胞-细胞粘附的关键调节剂.
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