在新生儿高氧性肺损伤后,FOXF2调节血管恒温所需的周细胞-内皮细胞信号传递
Fei Sun1,2,3, Yuchen Zhao4, Jonathan Do5
1Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China. feisun@scu.edu.cn.
Nature communications
|February 12, 2026
概括
在肺血管发育中,FOXF2对于细胞周细胞功能至关重要. 失去FOXF2会损害血管形成和气泡化,导致支气管肺功能失调.
科学领域:
- 肺血管生物学 肺血管生物学
- 新生儿肺部发育的过程
- 转录法规 转录法规
背景情况:
- 肺血管的发育对于膜化和肺功能至关重要.
- 血管发育的障碍有助于支气管肺功能障碍症 (BPD).
- 皮质细胞转录机制在支持肺内皮质中的作用尚不清楚.
研究的目的:
- 为了确定在产后肺发育中调节细胞周细胞功能的关键转录因子.
- 研究FOXF2在细胞周围细胞成熟中的作用及其对肺血管化的影响.
- 阐明FOXF2通过哪些机制影响周细胞-内皮细胞交叉.
主要方法:
- 在肺发育过程中和高氧损伤后,对心细胞中FOXF2表达的分析.
- 使用Pdgfrb-CreER小鼠在皮细胞中条件删除Foxf2.
- 转录和基因组分析 (ATAC-seq) 来评估FOXF2目标.
- 评估肺血管化,肺膜血管化和血管透性的情况.
主要成果:
- 在新生儿高氧后,FOXF2的表达在产后增加,并在新生儿高氧后减少.
- 细胞特异性Foxf2删除会导致增生,迁移受损和血管生成因子减少.
- FOXF2维持了亲血管性基因的染色质可访问性,并调节了对膜信号传递.
- 失去FOXF2会破坏细胞周细胞-内皮细胞的通讯,损害血管生成和膜化.
结论:
- FOXF2 是一个关键的转录因子,控制新生儿肺中的细胞细胞功能.
- FOXF2调节肺细胞驱动的血管,这对肺部发育和修复至关重要.
- 由FOXF2损失介导的细胞功能障碍有助于BPD的发病.
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