成年肺微血管原生细胞中mTOR信号的激活加快了肺衰老
Emma C Mason1, Swapna Menon2, Benjamin R Schneider1
1Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, Colorado, USA.
The Journal of clinical investigation
|October 24, 2023
概括
衰老肺部的mTOR信号失调会损害微血管原生细胞 (MVPCs),导致组织修复减少和肺气. 准mTOR可能会恢复MVPC功能和肺平衡.
科学领域:
- 肺研究研究 肺研究
- 血管生物学 血管生物学
- 衰老的研究研究.
背景情况:
- mTOR信号通路的重新激活和失调与衰老和慢性肺部疾病有关.
- 对肺微血管原生细胞 (MVPCs),毛细血管功能和组织平衡的具体影响仍然在很大程度上未知.
研究的目的:
- 研究mTOR信号通路在肺微血管原生细胞 (MVPC) 中的作用.
- 确定mTOR调节失调对MVPC功能,血管生成和肺组织恒温在衰老和慢性肺病中的影响.
主要方法:
- 使用了功能,血统和转录组分析.
- Abcg2用于丰富成年老鼠和人类肺部的组织居民MVPCs.
- 在MVPC中mTORC1激活与茎状,血管生成潜力和关键信号通路 (p53,Wnt) 相关研究.
主要成果:
- Abcg2在成年老鼠和人类肺部中识别出血管性,组织定居的MVPCs.
- 在人类和小鼠MVPC中mTORC1激活降低了茎度和血管生成潜力.
- mTORC1的激活破坏了p53和Wnt通路,导致膜毛细管结构和功能丧失.
结论:
- mTOR在维护MVPC功能和微血管利基恒温中发挥着至关重要的作用.
- 一个涉及MVPCs的基于细胞的机制有助于在肺衰老和肺气中损失组织结构.
- 研究结果表明mTOR是与年龄相关的肺部疾病的潜在治疗点.
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