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

我们研究了鞘氨醇1-磷酸（Sph-1-P）在血管生物学中的意义，并尝试了其在检验医学中的应用。以下是获得的主要结果。1)血管内皮细胞和平滑肌细胞中的EDG受体发现人脐静脉内皮细胞（HUVECs）和血管平滑肌细胞（SMCs）中EDG-5蛋白的表达分别较弱和丰富。一种EDG-5拮抗剂逆转了。抑制Sph-1-P对SMC迁移的影响，并进一步增强Sph-1-P对促生长HUVEC迁移的影响。因此，研究表明，EDG-55拮抗剂可以实现对血管细胞中Sph-1-P调节的迁移反应的特异性调节，EDG拮抗剂对Sph-1-P生物活性的操纵可能导致治疗应用于控制血管疾病。此外，SphlP通过EDG-5/Rho信号诱导冠状动脉SMCs收缩。2)肝细胞中的EDG受体sph -1- p被发现对大鼠肝细胞具有抗增殖作用，考虑到sph -1- p是许多细胞类型的有丝分裂原这一既定概念，这是一种异常现象。3) Sph-1-P测定采用Sph-1-P与邻苯二醛偶联，HPLC分离，荧光监测，建立了Sph-1-P测定体系。目前，我们正在努力确定其在检验医学中应用的最佳血浆取样条件。

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.