Role of HGF in the nervous system

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(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