Korhonen L, Sjöholm U, Takei N, Kern M A, Schirmacher P, Castrén E, Lindholm D
Department of Neuroscience Neurobiology, Uppsala University, Box 587, BMC, S-75123 Uppsala, Sweden.
Eur J Neurosci. 2000 Oct;12(10):3453-61. doi: 10.1046/j.1460-9568.2000.00260.x.
Hepatocyte growth factor-scatter factor (HGF) is expressed in different parts of the nervous system, and has been shown to exhibit neurotrophic activity. Here we show that c-Met, the receptor for HGF, is expressed in developing rat hippocampus, with the highest levels during the first postnatal weeks. To study the function of HGF, hippocampal neurons were prepared from embryonic rats and treated with different HGF concentrations. In these cultures, HGF increased the number of neurons expressing the 28-kDa calcium-binding protein (calbindin D) in a dose-dependent manner. The effect of HGF was larger than that observed with either brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3), and cotreatment of the cultures with HGF and the neurotrophins was additive with respect to calbindin D neurons. Besides affecting the number of neurons, HGF significantly increased the degree of sprouting of calbindin D-positive neurons, suggesting an influence on neuronal maturation. BDNF and NT-3 stimulated neurite outgrowth of calbindin D neurons to a much smaller degree. In contrast to calbindin D neurons, HGF did not significantly increase the number of neurons immunoreactive with the neurotransmitter gamma-aminobutyric acid (GABA) in the hippocampal cultures. Immunohistochemical studies showed that c-Met-, calbindin D- and HGF-immunoreactive cells are all present in the dentate gyrus and partly colocalize within neurons. These results show that HGF acts on calbindin D-containing hippocampal neurons and increases their neurite outgrowth, suggesting that HGF plays an important role for the maturation and function of these neurons in the hippocampus.
肝细胞生长因子-离散因子（HGF）在神经系统的不同部位表达，并已显示出具有神经营养活性。在此我们表明，HGF的受体c-Met在发育中的大鼠海马体中表达，在出生后的第一周内水平最高。为了研究HGF的功能，从胚胎大鼠制备海马神经元并用不同浓度的HGF进行处理。在这些培养物中，HGF以剂量依赖性方式增加了表达28 kDa钙结合蛋白（钙结合蛋白D）的神经元数量。HGF的作用大于脑源性神经营养因子（BDNF）或神经营养因子-3（NT-3）所观察到的作用，并且在培养物中用HGF和神经营养因子共同处理对钙结合蛋白D神经元具有累加效应。除了影响神经元数量外，HGF还显著增加了钙结合蛋白D阳性神经元的发芽程度，表明对神经元成熟有影响。BDNF和NT-3对钙结合蛋白D神经元的神经突生长刺激程度要小得多。与钙结合蛋白D神经元相反，HGF并没有显著增加海马培养物中与神经递质γ-氨基丁酸（GABA）免疫反应的神经元数量。免疫组织化学研究表明，c-Met、钙结合蛋白D和HGF免疫反应性细胞均存在于齿状回中，并且部分在神经元内共定位。这些结果表明，HGF作用于含有钙结合蛋白D的海马神经元并增加其神经突生长，表明HGF对海马中这些神经元的成熟和功能起重要作用。
