淋巴内皮mTORC1指导在淋巴血管生成期间代谢和发育信号
Fei Han1, Summer Simeroth2, Jie Zhu1
1Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Developmental cell
|May 8, 2025
概括
拉巴胺素复合体1 (mTORC1) 途径的机械性标调节营养代谢和PROX1表达,这对淋巴发育至关重要. mTORC1的丧失会损害淋巴毛细血管的生长和收集血管的分化.
科学领域:
- 血管生物学 血管生物学
- 细胞代谢 细胞代谢
- 发展生物学 发展生物学
背景情况:
- 淋巴内皮细胞 (LEC) 需要营养代谢来进行淋巴血管生成.
- PROX1的表达对于淋巴细胞的特异性至关重要.
- 目前尚不清楚LEC营养代谢与PROX1之间的分子联系.
研究的目的:
- 阐明关联营养代谢和LEC中的PROX1表达的分子机制.
- 研究mTORC1在调节新陈代谢程序中的作用,以及在淋巴血管生成过程中的PROX1.
主要方法:
- 使用了基因切除RAPTOR的小鼠模型,这是mTORC1的一个关键组成部分.
- 在小鼠和人类LEC上进行实验,以评估mTORC1抑制效应.
- 分析了PROX1,Myc,hexokinase 2 (HK2) 和谷氨酸酶 (GLS) 表达的变化.
- 进行了基因相互作用分析.
主要成果:
- 失去RAPTOR (mTORC1成分) 降低了PROX1的调节,并影响了淋巴毛细血管的生长和收集血管的分化.
- mTORC1的抑制降低了Myc,随后降低了HK2和GLS,从而抑制了糖解和谷氨酸溶解.
- 移除Myc或HK2/GLS会阻碍淋巴血管的形成.
- mTORC1对PROX1的调节独立于Myc-HK2/GLS信号传输.
- Myc和PROX1对于mTORC1调节的淋巴发育至关重要.
结论:
- mTORC1是对淋巴血管生成至关重要的代谢程序的关键调节者.
- mTORC1控制PROX1的表达,独立于Myc介导的代谢途径.
- 这项研究揭示了mTORC1是淋巴发育过程中LEC代谢和PROX1水平的中心协调者.
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