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Molecular cloning and characterization of HGF family members with neurotrophic activities

具有神经营养活性的 HGF 家族成员的分子克隆和表征

基本信息

批准号：
10680717
负责人：
FUNAKOSHI Hiroshi
金额：
$ 2.11万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10680717/
关键词：
Hepatocyte growth factor HGF c-Met HLP neurotrophic factor neuron Transgenic mice neurodegenerative disease クローニングトランスジェニック Sky Gas6 チロシンキナーゼ型受容体

项目摘要

(1) Expressional analysis of HGF and c-Met/HGF receptor in the nervous systemExpression of HGF and c-Met were examined by quantitative competitive RT-PCR and immunohitochemistry.(a) Cerebral cortex development; both HGF and c-Met was regulated in a dynamic fashion. Taken together with in vitro activities of HGF that accelerate survival, neurite, and migration, it is suggested that HGF may have critical role for the cortical layer formation.(b) Retinal development; both c-Met and HGF were expressed in retinal cells during development. Especially c-Met expression and in retinal neurons after eye opening and adult photoreceptor cells in adult, suggesting the activity dependent role of HGF in retina.(2) Neurotrophic activities of HGF in vitro. Neurotrophic activities, such as survival, neurite extension, proliferation in early neuroepithelial cells and migration promoting activities in different types of neural cells were examined.(3) Identification of HGF-like protein (HLP) as a novel neurotrophic factor. We first identify HLP as a neurotrophic factor using chicken peripheral ganglion cells.(4) Role of HGF on motor neurodegenerative disease using transgenic approach(a) Generation of HGF-overexpressing transgenic mice (NS-HGF-Tg) under the control of neuronal specific promoter. Generated mice were characterized.(b) Generation and characterization of double-transgenic mice of HGF-ALS-transgenic mice. By mating HS-HGF-Tg with ALS-transgenic mice, comparing with double-transgenic mice, single-transgenic mice or sister wild-type mice.

(1)HGF和c-Met/HGF受体在神经系统中的表达分析用定量竞争RT-PCR和免疫组化方法检测HGF和c-Met的表达。(a)大脑皮质发育; HGF和c-Met均以动态方式进行调节。考虑到肝细胞生长因子在体外的活性，加速生存，神经突，和迁移，这表明，肝细胞生长因子可能具有关键作用的皮质层的形成。(b)视网膜发育; c-Met和HGF在发育过程中在视网膜细胞中表达。尤其是c-Met在睁眼后的视网膜神经元和成年后的成年感光细胞中的表达，提示HGF在视网膜中的活性依赖性作用。(2)HGF的体外神经营养活性。检测神经营养活性，如存活、轴突延伸、早期神经上皮细胞的增殖和不同类型神经细胞的迁移促进活性。(3)HGF样蛋白（HLP）作为一种新的神经营养因子的鉴定。我们首先使用鸡外周神经节细胞鉴定HLP作为神经营养因子。(4)（a）在神经元特异性启动子控制下产生HGF过表达转基因小鼠（NS-HGF-Tg）。对生成的小鼠进行表征。(b)HGF-ALS转基因小鼠的双转基因小鼠的产生和表征。通过将HS-HGF-Tg与ALS转基因小鼠交配，与双转基因小鼠、单转基因小鼠和野生型小鼠进行比较。