源自内皮的血管新生信号诱导并维持再生性肺膜化
Bi-Sen Ding1, Daniel J Nolan, Peipei Guo
1Ansary Stem Cell Institute, Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
Cell
|November 1, 2011
概括
成人的肺再生涉及肺毛细体内皮细胞 (PCECs),产生刺激上皮原生细胞增殖的生长因子. 这一过程对于肺损伤后的肺膜形成至关重要.
科学领域:
- 肺部医学 肺部医学
- 再生生物学 再生生物学
- 细胞生物学 细胞生物学
背景情况:
- 成人肺部再生是一个复杂的过程,涉及协调的细胞反应.
- 单侧肺切除术 (PNX) 是一种用于研究剩余肺组织中的再生性肺膜化模型.
研究的目的:
- 为了确定关键的分子通路和细胞相互作用驱动成人的肺再生.
- 阐明肺毛细体内皮细胞 (PCEC) 和它们分泌的因子在膜生成中的作用.
主要方法:
- 使用单边肺切除术 (PNX) 的小鼠模型.
- 使用内皮特异性诱导性基因切除VEGFR2和FGFR1.1.
- 研究了MMP14的功能及其与EGFR信号的相互作用.
主要成果:
- PNX刺激PCECs产生血管新生因子,促进表皮原生细胞的增殖和胞生成.
- 在内皮细胞中的Vegfr2和Fgfr1的遗传切除损害了MMP14的产生和随后的膜化.
- 已经证明,MMP14通过揭露类似EGF的ectodomains来激活EGFR信号传递,这对于上皮细胞扩张至关重要.
结论:
- 在PCEC中VEGFR2和FGFR1的激活驱动着MMP14依赖的EGFR连接体的生物可用性,启动和维持胞生成.
- 准这种途径有可能用于肺再生的治疗干预.
- 在服用EGF或移植MMP14(+) PCEC时观察到肺功能恢复.
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