Role of HGF in the nervous system

(1)HGF在肌萎缩侧索硬化症及其胶质细胞增生症中的作用：我们先前已报道，HGF在神经系统中的过表达可以减轻脊髓运动神经元的死亡，运动纤维变性，改善运动功能，延长ALS转基因小鼠模型的生存时间。我们在这里证明了HGF不仅有能力减轻脊髓运动神经元的退化，还具有减轻脑干运动神经元的退化的能力，如舌下运动神经元和面运动神经元。此外，我们还证明了HGF可以减轻ALS模型小鼠的胶质细胞增多症(星形细胞增多症和微血管增多症)。此外，鞘内注射重组人HGF蛋白可以剂量依赖的方式延缓ALS转基因大鼠的疾病进展。应该注意的是，HGF即使在疾病开始时也会显示出有益的效果。这些发现增加了肝细胞生长因子可用于治疗肌萎缩侧索硬化症和相关疾病的可能性。(2)ro…HGF在少突胶质细胞发育中的作用：与HGF在神经元中的作用相反，HGF在少突胶质细胞发育中的作用鲜为人知。由于HGF及其受体c-Met基因敲除的小鼠是胚胎致死性的，我们利用重组HGF蛋白及其功能性阻断抗体在P7和P10脑内立体定向注射HGF来显示HGF在少突胶质前体细胞(OPC)中的作用，发现HGF促进少突胶质前体细胞的增殖，但抑制向少突胶质细胞的分化，少突胶质细胞表达突起生长的抑制分子。综上所述，HGF促进神经突起生长，且HGF在突起生长过程中水平较高，而在中介期水平较低，HGF可能在突起生长与少突胶质细胞发育的协调中发挥重要作用。(3)HGF样蛋白在原代小胶质细胞中的作用：我们首次提供了证据，证明HGF样蛋白(HLP)/巨噬细胞刺激蛋白(MSP)是HGF的结构相关蛋白，具有促进小胶质细胞迁移和调节细胞因子如IL-6、GM-CSF和离子的产生的能力。较少

(1) The role of HGF in amyotrophic lateral sclerosis and its gliosis : We have previously reported that overexpression of HGF in the nervous system can attenuate spinal motor neuron death, motor fiber degeneration, improve motor function and prolongs the life span of a transgenic mouse model of ALS. We here demonstrated that HGF has the ability to attenuate degeneration of not only spinal but also brain stem motor neurons, such as hypoglossal and facial motor neurons. In addition, we have demonstrated that HGF could attenuate gliosis (astrocytosis and micangliosis) in ALS model mice. Furthermore, intrathecal delivery of recombinant human HGF protein could attenuate the progression the disease in a transgenic rat model of ALS in a dose-dependent manner. It should be noted that HGF could show beneficial effect even when it is delivered from the onset of the disease. These findings raise the possibility that HGF could be used as a therapeutic agent for ALS and related disorders.(2) The ro … More le of HGF in oligodendrocyte development : In contrast to the role f HGF in neurons, the role of HGF in oligodendrocyte development is poorly understood. Since knockout mice of HGF and its receptor c-Met are embryonic lethal, we took advantage to use stereotaxic administration of recombinant HGF protein and its functional blocking antibody into the brain at P7 and P10 to show the role of HGF in oligodendrocyte precursor cells (OPCs) and found that HGF accelerates proliferation of OPCs while inhibits differentiation into oligodendrocytes, which express inhibitory molecules for neurite outgrowth. Taken together with the notion that HGF promotes neurite outgrowth and the level of HGF is high during the neurite outgrowth while low in the periods of mediation, HGF may play an important role in coordination of neurite out growth ad oligodendrocyte development.(3) The role of HGF-like protein in primary microglia: We have provided the first evidence that HGF-like protein (HLP) / macrophage stimulating protein (MSP), only the structural relative of HGF, has the ability to promote microglial migration and regulate production of cytokines, such as IL-6,GM-CSF and ions. Less