Functional consequences of S1P receptor modulation in rat oligodendroglial lineage cells
Functional consequences of S1P receptor modulation in rat oligodendroglial lineage cells
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DOI：
10.1002/glia.20576
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发表时间：
2007-12-01
期刊：
影响因子：
6.2
通讯作者：
Soliven, B.
中科院分区：
文献类型：
--
作者：
Jung, C. G.;Kim, H. J.;Soliven, B.
Fingolimod （FTY720）及其磷酸化形式FTY720P是鞘氨醇-1-磷酸（SIP）受体的调节剂，SIP受体是与细胞迁移和血管成熟相关的g蛋白偶联受体。FTY720在自身免疫性疾病（如多发性硬化症）及其动物模型中的疗效归因于其抑制淋巴细胞向靶器官的运输。在这项研究中，我们利用FTY720的活性磷酸化形式检测了SIP受体在培养的大鼠少突胶质细胞（OLGs）和OLG祖细胞（OPCs）中的作用。我们发现(1)FTY720P提高了血清戒断期间新生大鼠OLGs的存活率，这与细胞外信号调节激酶（ERK1/2）和Akt的磷酸化有关；(2) FTY720P以浓度依赖的方式调控OPC向OLGs的分化；(3) SIP受体受血小板衍生生长因子（PDGF）的差异调节，导致OPCs中S1P5下调，S1P1上调。此外，siRNA研究显示S1P1参与pdgf诱导的OPC有丝分裂发生。我们得出结论，S1P1和SIP5在少突胶质发育过程中起着不同的作用，可能在髓鞘再生过程中也起着不同的作用。(C) 2007 Wiley-Liss, Inc。
Fingolimod (FTY720) and its phosphorylated form FTY720P are modulators of sphingosine-1-phosphate (SIP) receptors , which are G-protein coupled receptors linked to cell migration and vascular maturation. The efficacy of FTY720 in autoimmune diseases such as multiple sclerosis and its animal models has been attributed to its inhibition of lymphocyte trafficking to target organs. In this study, we examined the role of SIP receptors in cultured rat oligodendrocytes (OLGs) and OLG progenitor cells (OPCs) using the active phosphorylated form of FTY720. We found that (1) FTY720P improves the survival of neonatal rat OLGs during serum withdrawal, which is associated with the phosphorylation of extracellular signal regulated kinases (ERK1/2) and Akt; (2) FTY720P regulates OPC differentiation into OLGs in a concentration-dependent manner; and (3) SIP receptors are differentially modulated by platelet-derived growth factor (PDGF) resulting in downregulation of S1P5 and upregulation of S1P1 in OPCs. In addition, siRNA studies revealed that S1P1 participates in PDGF-induced OPC mitogenesis. We conclude that S1P1 and SIP5 serve different functions during oligodendroglial development, and possibly during remyelination. (C) 2007 Wiley-Liss, Inc.