Roles of extracellular and intracellular sphingosine 1‐phosphate in cell migration
Roles of extracellular and intracellular sphingosine 1‐phosphate in cell migration
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DOI：
10.1111/j.1365-2443.2009.01295.x
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发表时间：
2009-05
期刊：
影响因子：
2.1
通讯作者：
Huan Yu;T. Okada;M. Kobayashi;D. M. Abo-elmatty;S. Jahangeer;Shun-ichi Nakamura
中科院分区：
文献类型：
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作者：
Huan Yu;T. Okada;M. Kobayashi;D. M. Abo-elmatty;S. Jahangeer;Shun-ichi Nakamura
1-磷酸鞘氨醇(S1P)是调节细胞运动的重要因子，作用于细胞内外。然而，S1P在控制细胞运动中的确切作用仍不清楚。在这里，我们描述了S1P在调节细胞运动中的作用，通过使用脂质体S1P转移技术将S1P分解为细胞内和细胞外的动作。在Boyden小室实验中，游离的S1P促进了细胞的定向运动，而脂质体S1P诱导了非定向的细胞运动。此外，用几种抑制剂抑制鞘氨醇激酶(SphK)1或用siRNA抑制该酶的表达，可以减少伤口愈合试验中伤口表面细胞的极性形成。此外，SphK抑制剂强烈抑制S1P诱导的细胞迁移。这些结果表明，细胞外S1P通过S1P受体促进细胞极性的形成，而细胞内产生的S1P本身作为细胞内介质促进非定向细胞运动，因此S1P以协调的方式促进细胞定向运动。
Sphingosine 1‐phosphate (S1P) is an important factor for the regulation of cell motility acting both inside and outside the cells. The precise role of S1P in the control of cell motility, however, remains unclear. Here we describe the roles of S1P in the regulation of cell motility by dissecting them into intracellular and extracellular actions using a liposomal S1P transfer technique. In a Boyden chamber assay free S1P enhanced directional cell movement, whereas liposomal S1P induced nondirectional cell movement. Furthermore, inhibition of sphingosine kinase (SphK) 1 by several inhibitors or knockdown of the enzyme expression by siRNA caused reduced wound‐faced cell polarity formation as assessed by wound‐healing assay. Moreover, S1P‐induced cell migration was strongly inhibited by SphK inhibitors. These results indicate that extracellular S1P acting through S1P receptors facilitates the formation of cell polarity, whereas S1P generated inside the cells functions as an intracellular mediator per se to enhance nondirectional cell movement, thus S1P enhances directional cell movement in a coordinated fashion.