通过mTORC2-PKC通路激活内心的机械力模式.
Yunfei Mu1,2,3,4, Shijia Hu1,2,3,4, Xiangyang Liu2,3,4
1Fudan University, Shanghai, China.
eLife
|February 11, 2025
概括
机械力量,而不仅仅是连接体,激活了心脏发育中的Notch信号. 这一过程对于内心模式和理解先天性心脏病至关重要.
科学领域:
- 心血管生物学 心血管生物学
- 发展生物学 发展生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 痕信号通过胚胎心脏的内皮转移到介质细胞转移 (EMT) 调节内心模式.
- 驱动内心的Notch通路激活的确切机制尚未完全理解.
研究的目的:
- 阐明心脏发育过程中内心脏中Notch激活的精确机制.
- 调查机械力和依赖联体路径在Notch信号传输中的作用.
主要方法:
- 在E9.5小鼠胚胎中利用过渡性心跳阻塞.
- 分析了Notch激活,Dll4表达和剪切应激对内心细胞的影响.
- 研究了下游的信号通路,包括mTORC2和PKC.
主要成果:
- 动脉内皮中的口激活取决于Dll4连接体.
- 降低内心脏中的Dll4产生了配体枯竭的场,允许剪切应力激活AVC和OFT中的Notch.
- 增加的剪切应力改变细胞膜脂质微域,激活mTORC2和PKC,促进Notch1裂变,而不依赖于强烈的连接体刺激.
结论:
- 机械力,特别是剪切应力,作为内心脏模式的主要提示.
- 研究结果提供了对源自内心缺陷的先天性心脏病的见解.
- 突出了心血管发育中的机械线索介导的Notch激活的新机制.
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