Sphingosine 1-phosphate induces angiogenesis: Its angiogenic action and signaling mechanism in human umbilical vein endothelial cells
Sphingosine 1-phosphate induces angiogenesis: Its angiogenic action and signaling mechanism in human umbilical vein endothelial cells
复制标题
DOI：
10.1006/bbrc.1999.1586
复制
发表时间：
1999-11-02
影响因子：
3.1
通讯作者：
Kwon, YG
中科院分区：
文献类型：
--
作者：
Lee, OH;Kim, YM;Kwon, YG
1-磷酸鞘氨醇（S1 P）是一种具有生物活性的鞘脂代谢产物，大量储存在血小板中，并在血小板活化时释放。最近，S1 P已被假定为在血管生成中的潜在作用。在这项研究中，我提供了几条证据表明S1 P具有血管生成活性。在体外，S1 P刺激人脐静脉内皮细胞（HUVECs）的DNA合成和趋化运动的剂量依赖性的方式，在1 μ M达到接近最大值。S1 P还显著诱导HUVECs在Matrigel上的管形成。小鼠基质胶栓塞实验表明，S1 P在体内促进血管生成。此外，HUVEC暴露于S1 P导致细胞外信号调节激酶（ERK）和p38丝裂原活化蛋白激酶（p38 MAPK）以百日咳毒素（PTX）敏感的方式快速激活。PTX预处理可完全阻断S1 P诱导的HUVEC迁移和小管形成。MEK抑制剂U 0126可显著抑制S1 P诱导的小管形成，但ERK和p38 MAPK的抑制对S1 P诱导的HUVEC迁移无影响。综上所述，这些结果表明，S1 P诱导血管生成主要通过G（i）蛋白偶联受体在内皮细胞，并表明，S1 P可能作为血小板诱导的血管生成的重要调节剂。(C)北京：科学出版社.
Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid metabolite abundantly stored in platelets and released upon platelet activation. Recently, S1P has been postulated for its potential roles in angiogenesis. In this study, me provided several lines of evidence showing that S1P has angiogenic activity. In vitro, S1P stimulated DNA synthesis and chemotactic motility of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner, reaching a near maximum at 1 mu M. S1P also significantly induced tube formation of HUVECs on Matrigel. Matrigel plug assay in mice revealed that S1P promotes angiogenesis in vivo. In addition, exposure of HUVECs to S1P led to rapid activation of extracellular signal-regulated kinases (ERKs) and p38 mitogen-activated protein kinase (p38 MAPK) in a pertussis toxin (PTX)-sensitive manner. Notably, HUVEC migration and tube formation in response to S1P were completely blocked by pretreatment with PTX, Further, the MEK inhibitor U0126 markedly inhibited S1P-induced tube formation but S1P-induced migration was not affected by inhibition of ERK and p38 MAPK. Taken together, these results indicate that S1P induces angiogenesis predominantly via G(i) protein-coupled receptors in endothelial cells and suggest that S1P may act as an important modulator of platelet-induced angiogenesis. (C) 1999 Academic Press.