Activation of CXCR7 Receptor Promotes Oligodendroglial Cell Maturation
Activation of CXCR7 Receptor Promotes Oligodendroglial Cell Maturation
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DOI：
10.1002/ana.22214
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发表时间：
2010-12-01
影响因子：
11.2
通讯作者：
Kuery, Patrick
中科院分区：
文献类型：
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作者：
Goettle, Peter;Kremer, David;Kuery, Patrick
目的：少突胶质前体细胞的分化是中枢神经系统髓鞘形成的关键，并受到多种外在和内在因素的影响。趋化因子是一类在哺乳动物中高度保守的小分子蛋白质，参与发育、组织稳态和修复过程中的多种生物学过程。我们研究了趋化因子CXCL 12是否影响少突胶质细胞和什么样的细胞分化/成熟过程是由这个molecular.Methods：实验性自身免疫性脑脊髓炎诱导使用髓鞘少突胶质细胞糖蛋白。免疫染色和定量基因表达分析用于研究2个目前已知的CXCL 12受体在少突胶质细胞上的表达。刺激培养的原代少突胶质前体细胞，以确定形态成熟和髓鞘表达的配体/受体相互作用的影响。进行阻断和抑制实验，以揭示身份的transmittingreceptor.Results：该分析揭示了CXCR 4以及CXCR 7的存在，并在体内和体外的细胞成熟是伴随着上调CXCR 7和下调CXCR 4。值得注意的是，在患病的脱髓鞘中枢神经系统中，CXCR 7表达维持在少突胶质细胞上，而CXCR 4不能被检测到。然后，我们证明了CXCL 12刺激促进培养的原代少突胶质细胞前体细胞的形态成熟以及它们的髓鞘表达。CXCR 7受体的药理学抑制被证明可以完全阻断CXCL 12依赖性作用。解释：我们的研究结果表明，CXCR 7受体的特异性激活可以提供一种手段，以促进少突胶质细胞分化的病变或损伤的中枢神经系统。神经网络2010;68：915-924
Objective: Differentiation of oligodendroglial precursor cells is crucial for central nervous system (re)myelination and is influenced by multiple extrinsic and intrinsic factors. Chemokines, a group of small proteins, are highly conserved among mammals and have been implicated in a variety of biological processes during development, tissue homeostasis, and repair. We investigated whether the chemokine CXCL12 influences oligodendrocytes and what cellular differentiation/maturation processes are controlled by this molecule.Methods: Experimental autoimmune encephalomyelitis was induced using myelin oligodendrocyte glycoprotein. Immunostainings and quantitative gene expression analysis were used to study expression of the 2 currently known CXCL12 receptors on oligodendroglial cells. Stimulation of cultured primary oligodendroglial precursor cells was performed to determine the impact of the ligand/receptor interaction on morphological maturation and on myelin expression. Blocking and suppression experiments were conducted to reveal the identity of the transmitting receptor.Results: This analysis revealed the presence of CXCR4 as well as CXCR7 and that cellular maturation in vivo and in vitro is accompanied by upregulation of CXCR7 and downregulation of CXCR4. Of note, in the diseased demyelinating central nervous system, CXCR7 expression is maintained on oligodendroglial cells, whereas CXCR4 could not be detected. We then demonstrated that CXCL12 stimulation promotes morphological maturation of cultured primary oligodendrocyte precursor cells as well as their myelin expression. Pharmacological inhibition of the CXCR7 receptor was shown to block CXCL12-dependent effects entirely.Interpretation: Our findings suggest that a specific activation of the CXCR7 receptor could provide a means to promote oligodendroglia differentiation in the diseased or injured central nervous system. ANN NEUROL 2010;68:915-924