Hepatocyte growth factor (HGF) promotes oligodendrocyte progenitor cell proliferation and inhibits its differentiation during postnatal development in the rat
Hepatocyte growth factor (HGF) promotes oligodendrocyte progenitor cell proliferation and inhibits its differentiation during postnatal development in the rat
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DOI：
10.1016/j.brainres.2007.02.045
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发表时间：
2007-05-25
期刊：
影响因子：
2.9
通讯作者：
Nakamura, Toshikazu
中科院分区：
文献类型：
--
作者：
Ohya, Wakana;Funakoshi, Hiroshi;Nakamura, Toshikazu
肝细胞生长因子（HGF）最初是作为肝细胞的有丝分裂原克隆的，并已被鉴定为多种神经元的神经营养因子。然而，很少有人尝试评估HGF在少突胶质细胞系细胞中的作用。本研究的目的是阐明HGF在这些细胞发育过程中的作用。在出生后第3天（P3）、P7和P14，大鼠纹状体中c-Met/HGF受体或磷酸化c-Met与NG 2或RIP的双重免疫染色显示，c-Met在酪氨酸残基上被磷酸化，从而在P3-P14的NG 2（+）少突胶质细胞祖细胞（OPC）和P14的RIP+少突胶质细胞中被激活。在P7和P10纹状体内注射重组人HGF，BrdU（+）/NG 2（+）细胞占NG 2（+）细胞总数的相对比例增加，而BrdU（+）/MBP+少突胶质细胞数量减少。Western blot分析显示，注射HGF后髓鞘碱性蛋白（MBP）表达下调。电镜观察显示，HGF处理后有髓神经纤维数量减少。此外，纹状体内给予抗HGF IgG可增加BrdU（+）/MBP+少突胶质细胞的数量。这些发现表明，肝细胞生长因子增加增殖的OPCs和减弱其分化成髓鞘少突胶质细胞，可能是通过有利于轴突生长，可能是抑制髓鞘抑制分子对少突胶质细胞。实时定量RT-PCR显示，从P7到P14，纹状体中HGF mRNA的下调可能有利于OPC分化为髓鞘少突胶质细胞。我们的研究结果表明，c-Met信号，连同HGF调节，在发育少突胶质细胞生成中起着重要的作用。(c)2007 Elsevier B. V.保留所有权利。
Hepatocyte growth factor (HGF) was initially cloned as a mitogen for hepatocytes and has been identified as a neurotrophic factor for a variety of neurons. However, few attempts have assessed the role of HGF in cells of oligodendrocyte lineage. The purpose of this study was to elucidate the role of HGF in such cells during development. Double immunostaining for either c-Met/HGF receptor or phospho-c-Met with either NG2 or RIP in rat striatum at postnatal day 3 (P3), P7, and P14 revealed that c-Met was phosphorylated on tyrosine residues and thereby activated in NG2(+) oligodendrocyte progenitor cells (OPCs) at P3-P14 and in RIP+ oligodendrocytes at P14. Intrastriatal injections of recombinant human HGF at both P7 and P10 revealed that the relative ratio of BrdU(+)/NG2(+) cells per total number of NG2(+) cells increased, while BrdU(+)/MBP+ oligodendrocyte numbers decreased. Western blot analysis showed a down-regulation of myelin basic protein (MBP) after HGF injection. Electron microscopy revealed that the numbers of myelinated nerve fibers decreased after HGF treatment. Furthermore, administration of anti-HGF IgG into the striatum increased the number of BrdU(+)/MBP+ oligodendrocytes. These findings demonstrated that HGF increases proliferation of OPCs and attenuates their differentiation into myelinating oligodendrocytes, presumably by favoring neurite outgrowth that may be inhibited by the myelin inhibitory molecules on oligodendrocytes. Down-regulation of HGF mRNA in the striatum from P7 to P14, as revealed by quantitative real-time RT-PCR, may be favorable for OPC differentiation into myelinating oligodendrocytes. Our findings suggest that c-Met signaling, together with HGF regulation, plays an important role in developmental oligodendrogenesis. (c) 2007 Elsevier B.V. All rights reserved.