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在体内,VE-cadherin的乌比基化调节炎症诱导的血管透性
Markus Wilkens1, Leonie Holtermann1, Ann-Kathrin Stahl1
1Max Planck Institute for Molecular Biomedicine, D-48149, Muenster, Germany.
EMBO reports
|August 7, 2024
概括
在炎症期间,VE-cadherin的乌比基化调节了内皮屏障功能. 突变的关键氨酸残留物阻断了VE-cadherin的内细胞分裂,并降低了小鼠的血管透性,突出了其在炎症反应中的作用.
科学领域:
- 内皮细胞生物学 内皮细胞生物学
- 细胞粘附 细胞粘附
- 炎症研究的研究.
背景情况:
- VE-cadherin对于内皮结的完整性和屏障功能至关重要.
- 对于VE-cadherin在炎症期间调节内皮壁透性的作用尚不完全理解.
研究的目的:
- 调查VE-cadherin在调节内皮质屏障功能中的作用 在体内炎症期间.
- 确定 VE-cadherin 上的特定 lysine 残留物是否参与其无处可见化和随后的血管透性的调节.
主要方法:
- 利用人类静脉内皮细胞 (HUVECs) 来研究VE-cadherin由组胺和血栓激发的全方位化.
- 在VE-cadherin lysine残留物 (K626/633R和KallR) 中发生突变的敲入小鼠模型生成.
- 在突变和野生类型小鼠中评估了组胺或LPS诱导的血管透性,以及VE-cadherin内细胞和溶酶体向.
主要成果:
- 组胺和血栓激发VE-cadherin在HUVEC中的泛化,依赖于氨酸残留物K626和K633.
- 阻断ubiquitination的突变也抑制了VE-cadherin的基因组胺诱导的内细胞分裂.
- 与野生类型小鼠相比,突变小鼠在对胰岛素或LPS的反应中表现出显著降低的血管透性.
- 发现氨酸残留物K626/633对于VE-cadherin的溶酶体向很重要.
结论:
- 在炎症期间,VE-cadherin的ubiquitination是调节内皮膜屏障透性的关键机制.
- 特定的氨酸残留物 (K626和K633) 对于VE-cadherin无化,内细胞化和随后的血管泄漏至关重要.
- 准VE-cadherin无处可见化通路可能为具有增加血管透性的炎症性疾病提供治疗策略.
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