Peng Hui, Huang Yunlong, Rose Jeremy, Erichsen David, Herek Shelley, Fujii Nobutaka, Tamamura Hirokazu, Zheng Jialin
Laboratory of Neurotoxicology, the Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha 68198-5215, USA.
J Neurosci Res. 2004 Apr 1;76(1):35-50. doi: 10.1002/jnr.20045.
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.
基质细胞衍生因子1（SDF-1）和趋化因子受体CXCR4在神经系统中高表达。基因敲除研究表明，SDF-1和CXCR4在胚胎发育过程中的小脑、海马和新皮质神经细胞迁移中均发挥重要作用。为扩展这些观察结果，研究人员检测了大鼠和人类神经祖细胞（NPC）中的CXCR4信号事件。我们的结果显示，CXCR4在大鼠和人类NPC中大量表达。此外，SDF-1α可使NPC中的肌醇1,4,5-三磷酸、细胞外信号调节激酶1/2、Akt、c-Jun氨基末端激酶水平升高，并使细胞内钙增加，而环磷酸腺苷减少。最后，SDF-1α可在体外诱导人类NPC趋化，提示CXCR4在NPC迁移中发挥功能性作用。CXCR4拮抗剂T140和G蛋白偶联受体失活剂百日咳毒素（PTX）均可消除这些事件。最终，本研究提示SDF-1α可通过CXCR4影响NPC功能，且CXCR4在NPC上具有功能活性。
