Pattern of CXCR7 Gene Expression in Mouse Brain Under Normal and Inflammatory Conditions.
Pattern of CXCR7 Gene Expression in Mouse Brain Under Normal and Inflammatory Conditions.
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在正常和炎症条件下，小鼠大脑中CXCR7基因表达的模式。
DOI：
10.1007/s11481-015-9616-y
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发表时间：
2016-03
期刊：
影响因子：
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通讯作者：
Miller RJ
中科院分区：
文献类型：
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作者：
Banisadr G;Podojil JR;Miller SD;Miller RJ
趋化因子基质细胞衍生因子-1(SDF-1)/CXCL12通过其G蛋白偶联受体CXCR4发挥作用，参与神经发生、神经调节、脑炎症、HIV-1脑病和肿瘤生长。CXCR7是SDF-1/CXCL12的替代受体。CXCR7缺陷小鼠的特征表明，CXCR7在胎儿内皮生物学、心脏发育和B细胞定位中发挥作用。尽管CXCR7具有配体结合特性，但它似乎并不像传统的GPCR那样发出信号。有人认为，CXCR7可能不是单独发挥作用的，而是与CXCR4一起发挥作用的。在这里，我们利用CXCR7-EGFP转基因小鼠研究了CXCR7受体在成年小鼠脑内的区域定位。我们发现，这些受体在嗅球、大脑皮层、海马区、室下区、下丘脑和小脑等不同的脑区都有表达。CXCR7的广泛表达与脑血管病变有关。利用细胞类型特异性标记，发现CXCR7在神经元、星形胶质细胞和少突胶质细胞前体细胞中表达。GAD阳性神经元在海马区有CXCR7表达。CXCR7在齿状回的表达包括表达巢蛋白、GFAP的细胞和似未成熟颗粒细胞的细胞。在实验性自身免疫性脑脊髓炎(EAE)小鼠中，CXCR7由SVZ内迁移的少突胶质细胞前体细胞表达。然后，我们用同时表达CXCR7-EGFP和SDF-1-MRFP的双转基因小鼠比较了SDF-1/CXCL12和CXCR7的分布。SDF-1/CXCL12和CXCR7在胼胝体、下丘脑和小脑的表达增强。总体而言，CXCR7在正常和病理神经系统中的表达表明SDF-1/CXCL12通过与CXCR7的相互作用介导了CXCR4不依赖的功能。
The chemokine stromal cell-derived factor-1 (SDF-1)/CXCL12 acting via its G-protein coupled receptor (GPCR) CXCR4 has been implicated in neurogenesis, neuromodulation, brain inflammation, HIV-1 encephalopathy and tumor growth. CXCR7 was identified as an alternate receptor for SDF-1/CXCL12. Characterization of CXCR7-deficient mice demonstrated a role for CXCR7 in fetal endothelial biology, cardiac development, and B-cell localization. Despite its ligand binding properties, CXCR7 does not seem to signal like a conventional GPCR. It has been suggested that CXCR7 may not function alone but in combination with CXCR4. Here, we investigated the regional localization of CXCR7 receptors in adult mouse brain using CXCR7-EGFP transgenic mice. We found that the receptors were expressed in various brain regions including olfactory bulb, cerebral cortex, hippocampus, subventricular zone (SVZ), hypothalamus and cerebellum. Extensive CXCR7 expression was associated with cerebral blood vessels. Using cell type specific markers, CXCR7 expression was found in neurons, astrocytes and oligodendrocyte progenitors. GAD-expressing neurons exhibited CXCR7 expression in the hippocampus. Expression of CXCR7 in the dentate gyrus included cells that expressed nestin, GFAP and cells that appeared to be immature granule cells. In mice with Experimental Autoimmune Encephalomyelitis (EAE), CXCR7 was expressed by migrating oligodendrocyte progenitors in the SVZ. We then compared the distribution of SDF-1/CXCL12 and CXCR7 using bitransgenic mice expressing both CXCR7-EGFP and SDF-1-mRFP. Enhanced expression of SDF-1/CXCL12 and CXCR7 was observed in the corpus callosum, SVZ and cerebellum. Overall, the expression of CXCR7 in normal and pathological nervous system suggests CXCR4-independent functions of SDF-1/CXCL12 mediated through its interaction with CXCR7.