通过YAP介导的ZO-1稳定,ECM刚度控制了内皮屏障的完整性
Miaomiao Chi1, Xiangyu Xu2,3, Yaning Zhao1
1Department of Ophthalmology, Peking University Third Hospital, Beijing, China.
Bioactive materials
|December 8, 2025
概括
细胞外基质软化通过影响ZO-1稳定性来破坏细胞结. YAP,FAK和Hippo通路相互作用来调节这个过程,为组织屏障工程提供了洞察力.
科学领域:
- 生物材料科学 生物材料科学
- 细胞生物学 细胞生物学
- 组织工程是组织工程.
背景情况:
- 细胞间结合的完整性对于组织屏障功能至关重要.
- 减少细胞外矩阵 (ECM) 刚度是障碍物功能障碍的已知触发因素.
- 连接ECM硬度与结合完整性的机制尚未完全理解.
研究的目的:
- 为了研究ECM刚度对角膜内皮细胞 (CEnC) 结合完整性的影响.
- 阐明ECM硬度诱导的屏障功能障碍背后的分子机制.
- 探索YAP,FAK和Hippo通路对ECM刚性的反应中的作用.
主要方法:
- 使用可调节的聚烯胺基凝来模拟不同的ECM刚度.
- 研究了矩阵软化对CEnC形态和紧结蛋白ZO-1定位的影响.
- 研究了YAP和ZO-1之间的相互作用,以及FAK和Hippo信号通路的相互作用.
- 采用计算建模来分析应力传播和细胞间隙形成.
主要成果:
- 矩阵软化在CEnCs的形态变化之前,并诱导结节分解.
- 软化ECM损害了ZO-1的膜局部化和稳定性.
- YAP 稳定 ZO-1 抵御无素-蛋白酶体降解.
- FAK和Hippo通路协同调节YAP活动,影响连接完整性.
- 计算模型揭示了导致细胞脱离的压力的时空动态.
结论:
- ECM 刚度是细胞结合完整性的关键调节者.
- YAP在稳定ZO-1中发挥着新的作用,对于维持组织屏障至关重要.
- FAK,Hippo信号和YAP之间的协调相互作用调解了细胞对ECM刚性的反应.
- 这些发现为开发工程生物材料提供了基础,以增强组织屏障功能.
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