在围产期高氧损伤后,TrkB信号传递促进了膜毛细血管血管生成
Qing Ma1,2,3, Hanxiang Liu1,4, Ming Liu1,2
1Key Laboratory of Birth Defects and Related Diseases of Woman and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China.
概括
大脑衍生神经营养因子 (BDNF) 激活TrkB信号,促进肺毛细血管干细胞的增殖和血管生成. 这一途径对于保护bronchopulmonary dysplasia (BPD) 的小鼠模型中的高氧损伤至关重要.
科学领域:
- 肺部医学 肺部医学
- 发展生物学 发展生物学
- 细胞信号传输 细胞信号传输
背景情况:
- 支气管肺功能障碍症 (BPD) 涉及血管生成受损和肺毛细血管密度降低.
- 在BPD模型中,周产期高氧损伤会降低肺毛细血管干细胞 (gCap细胞) 和热氨酸受体激酶B (TrkB) 的表达.
- 在BPD中TrkB信号传递在Chap细胞增殖和肺血管新生中的作用尚未完全理解.
研究的目的:
- 在BPD小鼠模型中,研究TrkB信号是否对围产期Chap细胞增殖和肺血管生成至关重要.
- 确定TrkB激活对于与早产相关的肺部疾病的治疗潜力.
主要方法:
- 使用了一种由围产期高氧损伤引起的BPD小鼠模型.
- 用脑衍生神经营养因子 (BDNF) 激活TrkB信号传递 in vivo 和 in vitro.
- 评估了内皮细胞的增殖,毛细血管的形成和 gCap 细胞数量.
- 研究了下游的信号通路,包括MAPK/ERK.
主要成果:
- 在体外,BDNF治疗增强了内皮细胞管的形成.
- 在体内BDNF治疗增加了CGAP细胞的增殖,并减轻了高氧化引起的CGAP细胞损失.
- TrkB抑制加剧了高氧诱导的血管损伤,并破坏了内皮管的形成.
- 鉴定出MAPK/ERK信号传递是TrkB在肺血管生成中的下游媒介.
结论:
- 在围产期肺损伤期间,TrkB信号传递对肺血管生成和CgAp细胞存活至关重要.
- 激活BDNF/TrkB促进了毛细体内皮细胞的增殖,并保持了气囊架构.
- 激活TrkB/MAPK/ERK信号提供了BPD和相关的早产婴儿肺部疾病的潜在治疗策略.
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