Stromal cell-derived factor 1-mediated CXCR4 signaling in rat and human cortical neural progenitor cells
Stromal cell-derived factor 1-mediated CXCR4 signaling in rat and human cortical neural progenitor cells
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DOI：
10.1002/jnr.20045
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发表时间：
2004-04-01
影响因子：
4.2
通讯作者：
Zheng, JL
中科院分区：
文献类型：
--
作者：
Peng, H;Huang, YL;Zheng, JL
基质细胞衍生因子1（SDF-1）和趋化因子受体CXCR 4在神经系统中高度表达。敲除研究表明，SDF-1和CXCR 4在胚胎发育期间的小脑、海马和新皮质神经细胞迁移中起重要作用。为了扩展这些观察结果，检查了大鼠和人神经祖细胞（NPC）中的CXCR 4信号传导事件。我们的研究结果表明，CXCR 4在大鼠和人NPC上大量表达。此外，SDF-1 alpha诱导NPC中1，4，5-三磷酸肌醇、细胞外信号调节激酶1/2、Akt、c-Jun N末端激酶和细胞内钙的水平增加，而它减少了环磷酸腺苷。最后，SDF-1 α在体外可诱导人NPC的趋化性，提示CXCR 4在NPC迁移中发挥功能性作用。T140（CXCR 4拮抗剂）和百日咳毒素（PTX）（G蛋白偶联受体的灭活剂）均可消除这些事件。最终，本研究表明SDF-1 α可以通过CXCR 4影响NPC功能，并且CXCR 4在NPC中具有功能。(C)2004 Wiley-Liss，Inc.
Stromal cell-derived factor 1 (SDF-1) and the chemokine receptor CXCR4 are highly expressed in the nervous system. Knockout studies have suggested that both SDF-1 and CXCR4 play essential roles in cerebellar, hippocampal, and neocortical neural cell migration during embryogenesis. To extend these observations, CXCR4 signaling events in rat and human neural progenitor cells (NPCs) were examined. Our results show that CXCR4 is expressed in abundance on rat and human NPCs. Moreover, SDF-1alpha induced increased NPCs levels of inositol 1,4,5-triphosphate, extracellular signal-regulated kinases 1/2, Akt, c-Jun N-terminal kinase, and intracellular calcium whereas it diminished cyclic adenosine monophosphate. Finally, SDF-1alpha can induce human NPC chemotaxis in vitro, suggesting that CXCR4 plays a functional role in NPC migration. Both T140, a CXCR4 antagonist, and pertussis toxin (PTX), an inactivator of G protein-coupled receptors, abrogated these events. Ultimately, this study suggested that SDF-1alpha can influence NPC function through CXCR4 and that CXCR4 is functional on NPC. (C) 2004 Wiley-Liss, Inc.