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A Method for Labeling Vasculature in Embryonic Mice
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血管发育的FGF依赖的代谢控制
Pengchun Yu1, Kerstin Wilhelm2, Alexandre Dubrac1
1Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, USA.
Nature
|May 4, 2017
概括
纤维细胞生长因子 (FGF) 信号通过控制内皮细胞代谢来调节血液和淋巴血管的发展. FGF信号通过HK2促进糖解,这对细胞增殖和迁移至关重要.
科学领域:
- 血管生物学
- 细胞代谢
- 分子信号
背景情况:
- 血液和淋巴血管对于组织氧化和液体平衡至关重要.
- 内皮细胞的发芽,迁移和增殖是血管网络组合的关键.
- 细胞代谢显著影响血管发育,VEGF信号已经得到充分研究,但FGF的作用不太清楚.
研究的目的:
- 研究纤维细胞生长因子 (FGF) 在血管发育和新陈代谢中的作用.
- 阐明FGF信号影响内皮细胞功能的分子机制.
主要方法:
- 研究了内皮细胞中的FGFR信号通路.
- 分析了c-MYC (MYC) 和六酶2 (HK2) 表达的调节.
- 使用了淘汰小鼠模型 (泛内皮和淋巴特异性HK2淘汰,Fgfr1/Fgfr3双突变).
- 评估HK2过度表达对FGF信号缺陷细胞的影响.
主要成果:
- FGFR信号极大地调节了血管的发育.
- FGF信号控制MYC表达,这反过来又调节了HK2.
- 降低HK2水平会影响内皮细胞的糖解,增殖和迁移.
- 在Fgfr1/Fgfr3突变体中发现Hk2淘汰现象血管缺陷.
- HK2过度表达部分挽救了FGF信号抑制引起的缺陷.
结论:
- FGF信号传递是内皮糖解的关键调节者.
- 这种依赖于FGF的代谢调节对于发育和成人血管生长至关重要.
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