Expression of hepatocyte growth factor and c-Met after spinal cord injury in rats
Expression of hepatocyte growth factor and c-Met after spinal cord injury in rats
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DOI：
10.1016/j.brainres.2007.03.022
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发表时间：
2007-06-02
期刊：
影响因子：
2.9
通讯作者：
Morishita, Ryuichi
中科院分区：
文献类型：
--
作者：
Shimamura, Munehisa;Sato, Naoyuki;Morishita, Ryuichi
由于肝细胞生长因子（HGF）在中枢神经系统的发育和病理状态中起着关键作用，我们研究了大鼠脊髓损伤（SCI）后HGF及其受体c-Met的mRNA和蛋白表达的长期变化。实时荧光定量RT-PCR检测显示，损伤后7天，损伤节段肝细胞生长因子mRNA表达明显增加，高峰出现在损伤后7天。c-met mRNA表达在脊髓损伤后第1天开始上调，第14天达高峰。虽然HGF和c-met mRNA在损伤节段中的表达上调逐渐降低，但表达水平的升高持续到SCI后56天。与HGF mRNA表达一致，HGF蛋白水平显著增加，主要在损伤区域，持续到SCI后56天。免疫组化结果显示，脊髓损伤后第14天和第56天，大部分星形胶质细胞表达HGF和c-Met。染色与有丝分裂指示剂，溴脱氧尿苷（BrdU），发现少量的BrdU掺入细胞共定位与HGF/GFAP阳性或c-Met/GFAP阳性细胞在14和56天。这些数据表明，HGF和c-Met在亚急性至慢性脊髓损伤阶段主要在损伤区域周围的反应性星形胶质细胞中上调。由于HGF在神经营养活性中起关键作用，因此HGF/c-Met信号系统的激活可能参与创伤后再生过程。(C)2007 Elsevier B. V.保留所有权利。
Since hepatocyte growth factor (HGF) plays a pivotal role in the development of the central nervous system and pathological conditions, we examined the long-term changes in the mRNA and protein expression of HGF and its receptor c-Met after spinal cord injury (SCI) in rats. HGF mRNA was significantly increased from 7 days after.SCI in the injured segment, and the peak was at 7 days after SCI as assessed by real-time RT-PCR. Importantly, c-met mRNA expression was up-regulated from I day after SCI, and reached a peak at 14 days after SCI. Although up-regulation of HGF and c-met mRNA expression in the injured segment gradually decreased, the increased expression level persisted until 56 days after SCI. Consistent with HGF mRNA expression, HGF protein level was significantly increased mainly in the injured region, which persisted until 56 days after SCI. Immunohistochemistry showed that most of GFAP-positive reactive astrocytes expressed HGF and c-Met both on 14 days and 56 days after SCI. Staining with the mitotic indicator, bromodeoxyuridine (BrdU), revealed that a small number of BrdU-incorporated cells were co-localized with HGF/ GFAP-positive or c-Met/GFAP-positive cells both on 14 and 56 days. These data suggest that HGF and c-Met were up-regulated mainly in the reactive astrocytes around the injured region in the subacute to chronic stage of spinal cord injury. Since HGF plays a critical role in neurotrophic activity, activation of the HGF/c-Met signaling system might be involved in the process of post-traumatic regeneration. (C) 2007 Elsevier B.V. All rights reserved.