在p21阳性细胞中诱导mTert可以抵消毛细血管稀疏和肺缩
Larissa Lipskaia1,2, Marielle Breau3, Christelle Cayrou3
1Institute for Lung Health, Justus Liebig University, Giessen, Germany.
EMBO reports
|February 29, 2024
概括
催化活性端粒酶 (TERT) 通过维持内皮原生细胞来预防与年龄相关的肺损伤. 这可以保护老年小鼠免受毛细血管损失和肺肺气.
科学领域:
- 分子生物学分子生物学
- 衰老研究研究 衰老研究
- 肺部医学 肺部医学
背景情况:
- 端粒缩短与衰老和肺部疾病有关.
- 端粒酶对于端粒维护至关重要.
- 人们越来越多地认识到端粒酶的非正规功能.
研究的目的:
- 研究端粒酶催化子单元 (TERT) 在衰老的肺内皮细胞中的作用.
- 探索催化活性与非活性TERT对肺衰老表型的影响.
- 为了确定TERT对肺肺复发症的保护机制.
主要方法:
- 在p21Cdkn1a促销器下生成了一个表达TERT或非活跃TERT (TERTCI) 的小鼠模型.
- 利用单细胞RNA测序进行肺部分析.
- 评估端粒长度,氧化损伤,内皮细胞衰老和毛细血管密度.
- 使用实验性肺瘤模型 (VEGFR2抑制,低氧).
主要成果:
- 在老老鼠肺中,TERT,但不是TERTCI,减少了短端粒,氧化损伤和内皮细胞衰老.
- 通过TERT和TERTCI减少了p21的水平,这表明非正规的功能.
- TERT抵消了CD34+毛细体内皮细胞和毛细体密度的与年龄相关的衰退.
- TERT的保护作用在实验性肺瘤模型中得到证实.
结论:
- 具有催化活性的TERT可以防止与年龄相关的肺肺复发症.
- TERT保护了毛细血管内皮原生细胞,防止了血管损失.
- TERT的作用超越了端粒维护,在衰老过程中保护肺血管.
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