Hepatocyte growth factor promotes endogenous repair and functional recovery after spinal cord injury
Hepatocyte growth factor promotes endogenous repair and functional recovery after spinal cord injury
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DOI：
10.1002/jnr.21372
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发表时间：
2007-08-15
影响因子：
4.2
通讯作者：
Kano, Hideyuki
中科院分区：
文献类型：
--
作者：
Kitamura, Kazuya;Iwanami, Akio;Kano, Hideyuki
许多使用神经营养因子或药物的治疗干预措施都集中在脊髓损伤（SCI）后的继发性变性，以减少受损区域，促进轴突再生和功能恢复。肝细胞生长因子（HGF）被认为是成熟肝细胞的有效丝裂原和组织损伤炎症反应的介质，最近被强调为中枢神经系统（CNS）中有效的神经营养和血管生成因子。在本研究中，我们发现在脊髓损伤急性期，内源性HGF的上调程度低于HGF受体c-Met的上调程度，并利用复制能力不强的单纯疱疹病毒-1 （HSV-1）载体将外源性HGF注入损伤脊髓，以确定HGF是否发挥有益作用并促进脊髓损伤后的功能恢复。这种治疗显著促进了脊髓损伤后神经元和少突胶质细胞的存活、血管生成、轴突再生和功能恢复。这些结果表明，HGF基因传递到受损脊髓具有多种有益作用，并增强脊髓损伤后的内源性修复。这是第一个证明HGF对脊髓损伤疗效的研究。(C) 2007 Wiley-Liss, Inc。
Many therapeutic interventions using neurotrophic factors or pharmacological agents have focused on secondary degeneration after spinal cord injury (SCI) to reduce damaged areas and promote axonal regeneration and functional recovery. Hepatocyte growth factor (HGF), which was identified as a potent mitogen for mature hepatocytes and a mediator of inflammatory responses to tissue injury, has recently been highlighted as a potent neurotrophic and angiogenic factor in the central nervous system (CNS). In the present study, we revealed that the extent of endogenous HGF up-regulation was less than that of c-Met, an HGF receptor, during the acute phase of SCI and administered exogenous HGF into injured spinal cord using a replication-incompetent herpes simplex virous-1 (HSV-1) vector to determine whether HGF exerts beneficial effects and promotes functional recovery after SCI. This treatment resulted in the significant promotion of neuron and oligodendrocyte survival, angiogenesis, axonal regrowth, and functional recovery after SCI. These results suggest that HGF gene delivery to the injured spinal cord exerts multiple beneficial effects and enhances endogenous repair after SCI. This is the first study to demonstrate the efficacy of HGF for SCI. (C) 2007 Wiley-Liss, Inc.