G-protein-coupled receptor S1P1 acts within endothelial cells to regulate vascular maturation
G-protein-coupled receptor S1P1 acts within endothelial cells to regulate vascular maturation
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DOI：
10.1182/blood-2003-02-0460
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发表时间：
2003-11-15
期刊：
影响因子：
20.3
通讯作者：
Proia, RL
中科院分区：
文献类型：
--
作者：
Allende, ML;Yamashita, T;Proia, RL
鞘氨醇-1-磷酸（S1 P）通过G蛋白偶联受体刺激信号通路，并触发多种细胞过程，包括生长，存活和迁移。在S1 P（1）受体缺陷的胚胎中，血管不完全被血管平滑肌细胞（VSMCs）覆盖，表明S1 P（1）受体调节血管成熟。由于S1 P（1）受体的表达并不局限于特定的细胞类型，因此尚不清楚S1 P（1）受体是否通过直接在VSMC中发挥作用或间接通过其在内皮细胞（EC）中的活性以细胞自主的方式控制VSMC对血管的覆盖。通过使用Cre/IoxP系统，我们仅在EC中破坏S1 P（1）基因。条件突变胚胎的表型与S1 P全面缺陷胚胎的表型相似（1）。因此，血管平滑肌细胞的血管覆盖是由内皮细胞中S1 P（1）受体的活性决定的。
Sphingosine-1-phosphate (S1P) stimulates signaling pathways via G-protein-coupled receptors and triggers diverse cellular processes, including growth, survival, and migration. In S1P(1) receptor-deficient embryos, blood vessels were incompletely covered by vascular smooth muscle cells (VSMCs), indicating the S1P(1) receptor regulates vascular maturation. Because S1P(1) receptor expression is not restricted to a particular cell type, it was not known whether the S1P(1) receptor controlled VSMC coverage of vessels in a cell-autonomous fashion by functioning directly in VSMCs or indirectly through its activity in endothelial cells (ECs). By using the Cre/IoxP system, we disrupted the S1P(1) gene solely in ECs. The phenotype of the conditional mutant embryos mimicked the one obtained in the embryos globally deficient in S1P(1). Thus, vessel coverage by VSMCs is directed by the activity of the S1P(1) receptor in ECs.