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在血管发育过程中对Hif-2alpha的内皮内在要求

Li-Juan Duan¹, Yahui Zhang-Benoit, Guo-Hua Fong

¹Center for Vascular Biology, Department of Cell Biology and Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Conn 06030-3501, USA.

|April 27, 2005

概括

低氧诱导因子-2alpha (Hif-2alpha) 对于小鼠血管发育至关重要. 内皮特异性Hif-2alpha表达能挽救血管缺陷,这表明内皮细胞对内皮细胞的内在要求.

科学领域:

发展生物学发展生物学
分子生物学分子生物学
遗传学是一个遗传学.

背景情况:

血管系统的发育涉及复杂的细胞-细胞通信.
确定基因是否在内在或外在调节血管发育至关重要.
低氧诱导因子-2alpha (Hif-2alpha) 对血管发育至关重要,但其细胞特异性作用尚不清楚.

研究的目的:

调查Hif-2alpha是否在血管发育的内皮细胞内本质上是必要的.
确定特定于内皮的Hif-2alpha恢复是否可以拯救Hif-2alpha缺陷胚胎中的血管缺陷.

主要方法:

胚胎干细胞 (ES) 介导的转基因方法,在Hif-2alpha-/-胚胎的血管内皮中表达Hif-2alphacDNA.
血管发育救援和胚胎存活率的评估.
在Hif-2alpha缺陷和救出的胚胎中对Tie-2基因表达的分析.

主要成果:

在E12.5.5.之前,Hif-2alpha-/-胚胎表现出严重的血管缺陷和胚胎致死性.
基因-2α的内皮特异性再表达挽救了血管发育至E14.5并改善了生存率.
在Hif-2alpha突变体中减少的Tie-2表达,通过Hif-2alpha再表达恢复.

结论:

在内皮细胞中,Hif-2alpha对适当的血管发育有内在的要求.
缺氧可能通过Hif-2alpha介导的Tie-2表达直接调节内皮功能.

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