Flow-regulated endothelial S1P receptor-1 signaling sustains vascular development.
Flow-regulated endothelial S1P receptor-1 signaling sustains vascular development.
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DOI：
10.1016/j.devcel.2012.07.015
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发表时间：
2012-09-11
影响因子：
11.8
通讯作者：
Hla, Timothy
中科院分区：
文献类型：
--
作者：
Jung, Bongnam;Obinata, Hideru;Galvani, Sylvain;Mendelson, Karen;Ding, Bi-sen;Skoura, Athanasia;Kinzel, Bernd;Brinkmann, Volker;Rafii, Shahin;Evans, Todd;Hla, Timothy
在血管生成过程中，新生的血管芽融合形成血管网络，从而实现有效的循环。稳定血管丛的机制尚不清楚。 1-磷酸鞘氨醇 (S1P) 是一种血源性脂质介质，参与血管和免疫系统的调节。在这里，我们描述了 G 蛋白偶联 S1P 受体-1 (S1P1) 稳定初级血管网络的机制。观察到从血管网络的成熟区域到生长的血管前沿的S1P1表达梯度。在缺乏内皮 S1P1 的情况下，粘附连接不稳定，屏障功能被破坏，血流受到干扰，导致异常血管过度萌芽。有趣的是，S1P1 对 S1P 以及层流剪切应力作出反应，以在体外和体内转导内皮细胞中的流介导的信号传导。这些数据表明，血流和循环 S1P 激活内皮 S1P1，以稳定血管的发育和稳态。
During angiogenesis, nascent vascular sprouts fuse to form vascular networks enabling efficient circulation. Mechanisms that stabilize the vascular plexus are not well understood. Sphingosine 1-phosphate (S1P) is a blood-borne lipid mediator implicated in the regulation of vascular and immune systems. Here we describe a mechanism by which the G protein-coupled S1P receptor-1 (S1P1) stabilizes the primary vascular network. A gradient of S1P1 expression from the mature regions of the vascular network to the growing vascular front was observed. In the absence of endothelial S1P1, adherens junctions are destabilized, barrier function is breached, and flow is perturbed resulting in abnormal vascular hypersprouting. Interestingly, S1P1 responds to S1P as well as laminar shear stress to transduce flow-mediated signaling in endothelial cells both in vitro and in vivo. These data demonstrate that blood flow and circulating S1P activate endothelial S1P1 to stabilize blood vessels in development and homeostasis.
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影响因子：
4
作者：
Dejana, Elisabetta;Orsenigo, Fabrizio;Lampugnani, Maria Grazia
通讯作者：
Lampugnani, Maria Grazia
影响因子：
56.9
作者：
Lee, MJ;Van Brocklyn, JR;Hla, T
通讯作者：
Hla, T
DOI：
10.1161/atvbaha.108.179663
发表时间：
2009-06-01
影响因子：
8.7
作者：
Ferrara, Napoleone
通讯作者：
Ferrara, Napoleone
影响因子：
20.3
作者：
Fantin, Alessandro;Vieira, Joaquim M.;Ruhrberg, Christiana
通讯作者：
Ruhrberg, Christiana
影响因子：
20.3
作者：
Allende, ML;Yamashita, T;Proia, RL
通讯作者：
Proia, RL