内皮细胞特异性FGD5参与血管修剪决定了小鼠新血管的命运
Caroline Cheng1, Remco Haasdijk, Dennie Tempel
1Molecular Cardiology Laboratory, Ee2389a, Thoraxcenter, Erasmus University Medical Center, Gravendijkwal 230, 3015 GE Rotterdam, Netherlands.
Circulation
|June 5, 2012
概括
研究人员发现了含有5 (FGD5) 的FYVE,RhoGEF和PH域作为血管修剪的关键调节者. 这种基因促进了通过亡去除多余的新血管,这对适当的血管网络发展至关重要.
科学领域:
- 血管生物学 血管生物学
- 分子遗传学 分子遗传学
- 细胞生物学 细胞生物学
背景情况:
- 血管新生对于发育和修复至关重要,形成最初的血管网络,需要重塑.
- 血管修剪是重塑的关键步骤,通过亡消除了多余的新血管.
- 二次血管网络发展的遗传调节者仍然在很大程度上是未知的.
研究的目的:
- 为了确定血管修剪的新型遗传调节者.
- 阐明二级血管网络形成背后的分子机制.
主要方法:
- 转录学方法用于识别内皮特异性基因.
- 功能丧失和功能增益研究 (体外和体内).
- 试验包括管道形成,大动脉环,涂层珠和小鼠视网膜模型.
主要成果:
- 确定了含有5 (FGD5) 的FYVE,RhoGEF和PH域,作为一个对血管修剪至关重要的内皮特异性基因.
- FGD5抑制了新血管化,并促进了由亡诱导的血管消灭.
- 在老年小鼠中,FGD5通过结合和激活cdc42来激活hey1-p53通路,这与内皮细胞亡和p21(CIP1) 水平相关.
结论:
- FGD5是一种新的血管修剪的遗传调节器.
- FGD5通过激活内皮细胞中的亡来起作用.
- 这一发现揭示了血管重塑的分子机制.
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