来自鼻状内皮的诱导性血管性信号是肝脏再生所需的
Bi-Sen Ding1, Daniel J Nolan, Jason M Butler
1Howard Hughes Medical Institute, Ansary Stem Cell Institute, and Department of Genetic Medicine, Weill Cornell Medical College, New York, New York 10065, USA.
Nature
|November 12, 2010
概括
肝脏的鼻状内皮细胞 (LSECs) 通过释放刺激肝细胞增殖的血管新生因子,启动肝脏再生. 这一过程由VEGFR2-Id1信号介导,对于在受伤后恢复肝脏质量至关重要.
科学领域:
- 血管生物学 血管生物学
- 肝病学 肝病学是一种肝病学.
- 再生医学是一种再生医学.
背景情况:
- 内皮细胞通过建立指导性血管,在器官生成和再生中发挥关键作用.
- 由内皮细胞分泌的血管分泌因子支持组织修复和再生,类似于它们在血液形成中的作用.
- 在成年人中,特定的内皮细胞促进器官再生的精确机制在很大程度上是未知的.
研究的目的:
- 阐明肝脏侧侧内皮细胞 (LSECs) 在部分肝切除术后启动和维持肝脏再生的机制.
- 为了确定特定的分子途径和参与LSEC介导肝脏再生的因素.
- 探索LSECs在促进肝脏再生方面的治疗潜力.
主要方法:
- 利用小鼠70%的部分肝切除模型来研究生理性肝脏再生.
- 研究了血管内皮生长因子受体-2 (VEGFR2) 和转录因子Id1在LSEC中的作用.
- 采用诱导性基因切除,体外共同培养和LSEC的内移植.
主要成果:
- LSECs,定义为VEGFR3 ((+) CD34 ((-) VEGFR2 (((+) VE-cadherin (((+) FactorVIII (((+) CD45 ((-),通过血管新生因子启动肝脏再生.
- 在LSEC中对VEGFR2的遗传除,通过抑制Id1上调节,损害了肝细胞增殖和肝脏质量复合.
- 在LSECs中的Id1缺陷减少了关键血管新生因子 (HGF,Wnt2) 的表达,阻碍了肝脏的再生.
- 在体外和体内研究表明,LSEC中的VEGFR2-Id1激活刺激肝细胞的增殖和再生.
结论:
- 在LSEC中VEGFR2-Id1介导的信号传递对于通过诱导性血管生成和血管因子释放 (Wnt2,HGF) 启动肝脏再生至关重要.
- 通过LSECs的VEGFR2-Id1依赖的增殖性血管生成,在受伤后重建肝脏质量.
- 工程LSEC与肝细胞的治疗性共同移植为持久的肝脏再生提供了一个有希望的策略.
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