Role of PFKFB3-Driven Glycolysis in Vessel Sprouting
Role of PFKFB3-Driven Glycolysis in Vessel Sprouting
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DOI：
10.1016/j.cell.2013.06.037
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发表时间：
2013-08-01
期刊：
影响因子：
64.5
通讯作者：
Carmeliet, Peter
中科院分区：
文献类型：
--
作者：
De Bock, Katrien;Georgiadou, Maria;Carmeliet, Peter
内皮细胞（ECs）通过迁移尖端和增殖茎的血管发芽是由遗传信号（如Notch）控制的，但代谢是否也调节这一过程尚不清楚。在这里，我们发现内皮细胞依赖于糖酵解而不是氧化磷酸化来产生ATP，并且内皮细胞中糖酵解激活剂PFKFB3的缺失会损害血管的形成。在机制上，PFKFB3不仅调节EC增殖，还控制丝状足/板足的形成和定向迁移，部分是通过与F-actin在运动突起中区隔。体外和体内花芽实验进一步表明，PFKFB3过表达会抑制Notch的前茎活性，而PFKFB3缺乏会在Notch阻断后破坏尖端细胞的形成，这表明糖酵解调节血管分支。
Vessel sprouting by migrating tip and proliferating stalk endothelial cells (ECs) is controlled by genetic signals (such as Notch), but it is unknown whether metabolism also regulates this process. Here, we show that ECs relied on glycolysis rather than on oxidative phosphorylation for ATP production and that loss of the glycolytic activator PFKFB3 in ECs impaired vessel formation. Mechanistically, PFKFB3 not only regulated EC proliferation but also controlled the formation of filopodia/lamellipodia and directional migration, in part by compartmentalizing with F-actin in motile protrusions. Mosaic in vitro and in vivo sprouting assays further revealed that PFKFB3 overexpression overruled the pro-stalk activity of Notch, whereas PFKFB3 deficiency impaired tip cell formation upon Notch blockade, implying that glycolysis regulates vessel branching.