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在小鼠胚胎和新生儿发育过程中,TRAF7是血管完整性的重要调节剂
Erdyni N Tsitsikov1, Khanh P Phan1, Yufeng Liu1
1Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
iScience
|August 16, 2023
概括
瘤坏死因子受体相关因子7 (TRAF7) 对于内皮细胞完整性和生存至关重要,它调节MEKK3-MEK5-ERK5通路. TRAF7和SCRIB是这种血流诱导的信号级联的关键上游组件.
科学领域:
- 心血管生物学 心血管生物学
- 分子和细胞生物学分子和细胞生物学
- 内皮细胞信号传递
背景情况:
- 血液流动诱导剪切应力,激活内皮细胞中的信号通路.
- MEKK3-MEK5-ERK5通路对于血管发育和完整性至关重要.
- 这一途径中瘤亡因子受体相关因子7 (TRAF7) 的作用以前是未知的.
研究的目的:
- 研究TRAF7在切削应力响应的MEKK3-MEK5-ERK5信号通路中的作用.
- 为了确定TRAF7相互作用蛋白在这个途径.
- 阐明TRAF7在内皮细胞信号传递和血管完整性中的功能.
主要方法:
- 在小鼠中向删除TRAF7基因.
- 对TRAF7缺陷胚胎的胚胎死亡率和血管缺陷的分析.
- 在TRAF7缺陷模型中评估基因表达,包括Klf2.
- 同免疫沉测试以确定TRAF7相互作用蛋白.
- 使用培养内皮细胞进行体外研究,以检查ERK5酸化.
主要成果:
- 缺少TRAF7的胚胎由于内皮完整性受损而表现出中期死亡率.
- 在缺乏TRAF7的胚胎中观察到转录因子Klf2的减少表达.
- 在产后小鼠中,TRAF7的删除导致严重的脑出血.
- 发现TRAF7与平面细胞极性蛋白SCRIB结合.
- 对TRAF7或SCRIB的下调抑制了内皮细胞中流体剪切应力诱导的ERK5酸化.
结论:
- TRAF7对于胚胎血管发育和维持内皮质完整性至关重要.
- 在剪切应力激活的MEKK3-MEK5-ERK5信号通路中,TRAF7起着至关重要的作用.
- TRAF7和SCRIB的功能是这个重要的血管信号通路的上游组件.
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