Functional response to SDF1α through over-expression of CXCR4 on adult subventricular zone progenitor cells
Functional response to SDF1α through over-expression of CXCR4 on adult subventricular zone progenitor cells
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DOI：
10.1016/j.brainres.2008.06.013
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发表时间：
2008-08-21
期刊：
影响因子：
2.9
通讯作者：
Zhang, Zheng Gang
中科院分区：
文献类型：
--
作者：
Liu, Xian Shuang;Chopp, Michael;Zhang, Zheng Gang
趋化因子受体 CXCR4 及其配体、基质细胞衍生因子 1 α (SDF1 α) 调节中风后神经母细胞向缺血边界迁移。利用损失函数和增益函数，我们研究了 CXCR4/SDF1 α 对神经祖细胞的生物学效应。用大鼠 CXCR4-pLEGFP-C1 和 pSIREN-RetroQ-CXCR4-siRNA 逆转录病毒载体转染来自成年大鼠室下区 (SVZ) 的神经祖细胞。迁移测定分析表明，与空载体相比，siRNA 对 CXCR4 的抑制显着降低了细胞迁移，表明 CXCR4 介导神经祖细胞运动。当神经祖细胞在含有 bFGF (20 ng/ml) 的生长培养基中培养时，与对照组 (54.0%) 相比，CXCR4 的过表达显着降低了细胞增殖，通过溴脱氧尿苷 + (BrdU+) 细胞数量 (26.4%) 来衡量。将高浓度的 SDF1 α (500 ng/ml) 添加到过度表达 CXCR4 的祖细胞中，可将细胞增殖逆转回对照水平 (57.6%)。免疫染色分析表明，当神经祖细胞在分化培养基中培养时，CXCR4 的过度表达或抑制都不会改变神经元和星形胶质细胞的数量。这些体外结果表明，CXCR4/SDF1 α 主要调节成体神经祖细胞运动，但不调节分化，而在 SDF1 α 缺失的情况下 CXCR4 的过度表达会降低神经祖细胞增殖。 (C) 2008 Elsevier B.V. 保留所有权利。
The chemokine receptor CXCR4 and its ligand, stromal cell derived factor-1 alpha (SDF1 alpha) regulate neuroblast migration towards the ischemic boundary after stroke. Using loss- and gain-function, we investigated the biological effect of CXCR4/SDF1 alpha on neural progenitor cells. Neural progenitor cells, from the subventricular zone (SVZ) of the adult rat, were transfected with rat CXCR4-pLEGFP-C1 and pSIREN-RetroQ-CXCR4-siRNA retroviral vectors. Migration assay analysis showed that inhibition of CXCR4 by siRNA significantly reduced cell migration compared to the empty vector, indicating that CXCR4 mediated neural progenitor cell motility. When neural progenitor cells were cultured in growth medium containing bFGF (20 ng/ml), over-expression of CXCR4 significantly reduced the cell proliferation as measured by the number of bromodeoxyuridine+ (BrdU+) cells (26.4%) compared with the number in the control group (54.0%). Addition of a high concentration of SDF1 alpha (500 ng/ml) into the progenitor cells with over-expression of CXCR4 reversed the cell proliferation back to the control levels (57.6%). Immunostaining analysis showed that neither over-expression nor inhibition of CXCR4 altered the population of neurons and astrocytes, when neural progenitor cells were cultured in differentiation medium. These in vitro results suggest that CXCR4/SDF1 alpha primarily regulates adult neural progenitor cell motility but not differentiation, while over-expression of CXCR4 in the absence of SDF1 alpha decreases neural progenitor cell proliferation. (C) 2008 Elsevier B.V. All rights reserved.