里克托诱导AKT信号,以调节淋巴形成的过程
bioRxiv : the preprint server for biology
|July 3, 2023
概括
猛素复合体2 (mTORC2) 信号传递的哺乳动物目标,特别是其组成部分RICTOR,对于淋巴形成至关重要. AKT的RICTOR激活防止FOXO1核积累,促进门的发展和维护.
科学领域:
- 血管生物学 血管生物学
- 细胞信号传递 细胞信号传递
- 机械转导是指机械转导的过程.
背景情况:
- 淋巴对于防止淋巴回流和维持淋巴系统功能至关重要.
- 控制淋巴形成的基因突变与先天性淋巴有关.
- 淋巴的发育是通过PI3K/AKT通路由振荡剪切应力 (OSS) 调节的.
研究的目的:
- 研究mTORC2的关键组成部分RICTOR在淋巴形成中的作用.
- 阐明RICTOR影响AKT激活和门特异性基因表达的信号机制.
主要方法:
- 在小鼠淋巴内皮细胞 (LECs) 中Rictor的遗传删除.
- 在静态和流动条件下,RICTOR 在人体淋巴内皮细胞 (hdLEC) 中进行敲除.
- 分析AKT激活,形成基因表达和FOXO1核定位.
- 在活体中通过删除Rictor淘汰小鼠中的Foxo1进行救援实验.
主要成果:
- 里克托的胚胎和产后删除显著减少了淋巴的数量,并损害了收集淋巴血管的成熟.
- RICTOR knockdown降低了AKT激活和膜基因表达,取消了流动诱导的上调.
- 里克托删除导致核FOXO1活性增加,这是一个抑制门形成的抑制剂.
- 在Rictor淘汰赛小鼠中的Foxo1缺失恢复了淋巴形成.
结论:
- 雷克托信号传递对于淋巴的发育和维护至关重要.
- RICTOR激活AKT,这反过来又抑制了压器FOXO1.1的核积累.
- 这一途径代表了对淋巴血管系统至关重要的机械转导的新机制.
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