The significance of sphingosine 1-phosphate in vascular biology and its application to laboratory

我们研究了1-磷酸鞘氨醇（Sph-1-P）在血管生物学中的意义，并尝试将其应用于实验医学。主要研究结果如下：1）血管内皮细胞和平滑肌细胞中EDG受体的研究人脐静脉内皮细胞（HUVECs）和血管平滑肌细胞（SMCs）中EDG-5蛋白的表达分别较弱和较高。EDG-5拮抗剂逆转了这种情况。Sph-1-P抑制SMC迁移，并进一步增强Sph-1-P-stunulatecl HUVEC迁移。因此，表明血管细胞中Sph-1-P调节的迁移反应的特异性调节可以通过EDG-55拮抗剂实现，并且通过EDG拮抗剂操纵Sph-1-P生物活性可以导致控制血管疾病的治疗应用。2）肝细胞EDG受体Sph-1-P对大鼠肝细胞增殖具有抑制作用，考虑到Sph 1-P在许多细胞类型中是促分裂原的既定概念，这是一个例外的现象。通过SphIP与邻苯二甲醛偶联，然后用HPLC分离和荧光监测来测定P含量。现在我们正试图确定最佳的血浆采样条件，其应用于实验室医学。

We have examined the significance of sphingosine 1-phosphate (Sph-1-P) in vascular biology, and tried its application into laboratory medicine. Followings are the main results obtained.1)EDG receptors in vascular endothelial cells and smooth muscle cellsHuman umbilical vein endothelial cells (HUVECs) and vascular smooth muscle cells (SMCs) were found to express EDG-5 protein weakly and abundantly, respectively. An EDG-5 antagonist reversed the. inhibitory effect of Sph-1-P on SMC migration, and further enhanced Sph-1-P-stunulatecl HUVEC migration. Accordingly, it was indicated that specific regulation of Sph-1-P-modulated migration responses in vascular cells can be achieved by EDG-55 antagonists and that manipulation of Sph-1-P biological activities by the EDG antagonist may lead to a therapeutical application to control vascular diseases. Furthermore, SphlP was found to induce the contraction of coronary artery SMCs through the EDG-5/Rho signaling.2) EDG receptors in hepatocytesSph-1-P was found to exert an anti-proliferative effect on rat hepatocytes, which is an exceptional phenomenon considering an established concept that Sph1-P is a mitogen in many cell types.3) Sph-1-P assayWe have.established the Sph-1-P assay system by SphlP coupling with o'phthalaldehyde, followed by separation with HPLC and fluorescence monitoring. Now we are trying to determine the best plasma sampling conditions for its application to laboratory medicine.