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德尔塔像4通过DLL4-NOTCH-CLDN5通路调节脑血管发育和内皮完整性,易受新生儿高氧化症的影响
Xingrao Ke1, Sheng Xia1, Wei Yu1
1Department of Pediatrics Division of Neonatology, Children's Mercy, Kansas City, MO, USA.
The Journal of physiology
|April 18, 2024
概括
德尔塔像4 (DLL4) 对于发展大脑血管和维持血脑屏障至关重要. 新生儿高氧降低DLL4,可能会损害早产婴儿的大脑发育.
科学领域:
- 神经科学是一个神经科学.
- 发展生物学 发展生物学
- 血管生物学 血管生物学
背景情况:
- 人们对大脑血管化的机制知之甚少.
- 德尔塔像4 (DLL4) 是一个Notch连接体,是血管发育的关键调节者.
- 产后高氧症可以破坏大脑血管的发育和功能.
研究的目的:
- 研究DLL4在小鼠脑血管发育中的作用.
- 为了确定产后高氧化对大脑内皮细胞 (EC) DLL4表达的影响.
- 阐明EC中DLL4调节的下游信号通路.
主要方法:
- 使用Dll4+/+和Dll4+/LacZ小鼠研究DLL4表达模式.
- 使用人类大脑微血管内皮细胞进行了体外研究.
- 在暴露于产后高氧化的小鼠大脑EC中分析了Dll4和Claudin 5 (CLDN5) 表达.
主要成果:
- 在未成熟的大脑中,DLL4主要以EC表达.
- DLL4缺乏导致异常的大脑微血管和增加血管透性.
- DLL4不足通过NOTCH-NICD-RBPJ-CLDN5通路损害了内皮完整性,降低了CLDN5.5的调节.
- 新生儿高氧暴露减少DLL4和CLDN5表达在发展小鼠大脑EC.
结论:
- DLL4对于大脑血管发育和血脑屏障完整性至关重要.
- 新生儿高氧症抑制了DLL4信号传输.
- 降低EC中的DLL4信号可能会导致高氧暴露的新生儿的大脑发育受损.
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