Enhancement of sphingosine 1-phosphate-induced migration of vascular endothelial cells and smooth muscle cells by an EDG-5 antagonist
Enhancement of sphingosine 1-phosphate-induced migration of vascular endothelial cells and smooth muscle cells by an EDG-5 antagonist
复制标题
DOI：
10.1016/s0006-291x(02)02671-2
复制
发表时间：
2002-12-06
影响因子：
3.1
通讯作者：
Ozaki, Y
中科院分区：
文献类型：
--
作者：
Osada, M;Yatomi, Y;Ozaki, Y
1-磷酸鞘氨醇（Sph-I-P）是一种具有生物活性的溶血磷脂，通过与内皮细胞分化基因（EDG）/S1 P家族G蛋白偶联受体相互作用，发挥细胞间介质的作用。在这项研究中，JTE-013，一种特异性拮抗剂的迁移抑制受体EDG-5，对Sph-I-P引起的反应，在人脐静脉内皮细胞（HUVECs）和血管平滑肌细胞（SMCs），这表达EDG-5蛋白弱和丰富，分别检查。该吡唑并吡啶化合物逆转了Sph-1-P对SMC迁移的抑制作用，并进一步增强了Sph-1-P刺激的HUVEC迁移。相反，其对Sph-I-P诱导的细胞内Ca 2+动员的作用是边际的。我们的研究结果表明，Sph-1-P调节的迁移反应在血管细胞中可以实现EDG-5拮抗剂和Sph-1-P的生物活性的操纵每个EDG拮抗剂可能会导致治疗应用，以控制血管疾病。(C)2002 Elsevier Science（美国）。All rights reserved.
Sphingosine 1-phosphate (Sph-1-P), a bioactive lysophospholipid capable of inducing a wide spectrum of biological responses, acts as an intercellular mediator, through interaction with the endothelial differentiation gene (EDG)/S1P family of G protein-coupled receptors. In this study, the effects of JTE-013, a specific antagonist of the migration-inhibitory receptor EDG-5, on Sph-1-P-elicited responses were examined in human umbilical vein endothelial cells (HUVECs) and vascular smooth muscle cells (SMCs), which expressed EDG-5 protein weakly and abundantly, respectively. This pyrazolopyridine compound reversed the inhibitory effect of Sph-1-P on SMC migration and further enhanced Sph-1-P-stimulated HUVEC migration. In contrast, its effect on Sph-1-P-induced intracellular Ca2+ mobilization was marginal. Our results indicate that specific regulation of Sph-1-P-modulated migration responses in vascular cells can be achieved by EDG-5 antagonists and that manipulation of Sph-1-P biological activities by each EDG antagonist may lead to a therapeutical application to control vascular diseases. (C) 2002 Elsevier Science (USA). All rights reserved.