内细胞通路和动氨酸重塑 介于Everolimus诱导的VE-Cadherin失调和屏障功能障碍
Ken D Brandon1, Yoshi Chettri1, Azkah Anjum1
1Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.
Cellular and molecular bioengineering
|February 20, 2026
概括
埃弗罗利斯 (EVL) 通过引起VE-cadherin内部化和降解来破坏内皮屏障功能,影响细胞结合和细胞骨组织. 这项研究揭示了EVL诱导的血管功能障碍背后的分子机制.
科学领域:
- 内皮细胞生物学 内皮细胞生物学
- 血管生物学 血管生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 血管内皮卡德林 (VE-cadherin) 对于内皮粘附结和血管完整性至关重要.
- 内皮屏障功能障碍 (EBD) 是拉帕素类似物如Everolimus (EVL) 的已知副作用.
- 连接EVL与EBD的精确分子机制尚不清楚.
研究的目的:
- 调查Everolimus (EVL) 如何影响VE-cadherin组织,贩运,细胞骨结构和内皮细胞中的屏障功能.
- 为了阐明参与EVL诱导的内皮壁障碍功能障碍的细胞通路.
主要方法:
- 人类静脉内皮细胞 (HUVECs) 用EVL进行治疗.
- 使用共聚焦显微镜评估VE-cadherin组织.
- 细胞骨的变化通过F-actin异性质分析.
- 内细胞分裂,溶酶体降解和戈尔吉贩运在药理上被抑制.
- 用TEER和德克斯透度测试测量了内皮屏障功能.
主要成果:
- EVL导致了VE-cadherin的时间依赖性破坏,增加了点状结.
- 抑制内细胞分裂或溶酶体降解部分保留了VE-cadherin连续性.
- 戈尔吉通路的破坏阻碍了VE-cadherin的恢复.
- EVL诱导了细胞骨重塑和显著损害了内皮屏障功能,增加了透性.
结论:
- 埃弗罗利斯通过VE-cadherin内部化和溶酶体降解,损害了内皮屏障的完整性.
- 细胞骨重塑和戈尔吉介导的贩运在EVL诱导的EBD中起着重要作用.
- 这些发现为基于rapalog的mTOR抑制对血管的影响提供了机械的见解.
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