内皮1的水平和分布是通过ZFP36衰变蛋白进行后转录控制的
Hannah L Sunshine1, Andrew C Cicchetto2, Karolina Elżbieta Kaczor-Urbanowicz3
1Molecular, Cellular, and Integrative Physiology Graduate Program, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Cell and Development Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Cell reports
|December 29, 2023
概括
血管内皮生长因子 (VEGF) 刺激指蛋白36 (ZFP36) 抑制Jagged1 (JAG1) mRNA. 这种调节确保了对受控的血管形成 (血管生成) 进行适当的Notch信号.
科学领域:
- 分子生物学分子生物学
- 发展生物学 发展生物学
- 细胞生物学 细胞生物学
背景情况:
- 血管形态发生依赖于精确的诺奇信号梯度.
- 在血管中,Jagged1 (JAG1) 分隔并未得到充分理解.
研究的目的:
- 研究血管发育中的Jagged1 (JAG1) 表达的调节.
- 阐明指蛋白36 (ZFP36) 在控制JAG1水平和血管生成中的作用.
主要方法:
- 研究了ZFP36在内皮细胞中对Jag1mRNA的调节.
- 使用了体外血管生成试验和Zfp36缺乏的小鼠模型.
- 分析了Notch信号通路组件和血管模式.
主要成果:
- 血管内皮生长因子 (VEGF) 诱导ZFP36,一种RNA结合蛋白.
- ZFP36直接针对Jag1mRNA进行衰变,抑制了JAG1的水平.
- 缺乏ZFP36的内皮细胞表现出增加的JAG1和增强的血管发芽.
- 在小鼠中Zfp36缺乏导致JAG1错误模式和视网膜血管系统中改变的Notch信号.
结论:
- 在发芽血管生成过程中,VEGF诱导的ZFP36充当了JAG1的负调节者.
- 这种涉及ZFP36和JAG1的前循环对于保持适当的Notch信号水平至关重要.
- 这些发现揭示了一种控制血管模式和血管生成的新机制.
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