Role of hepatocyte growth factor in the pathoetiology of Alzheimer's disease

肝细胞生长因子在阿尔茨海默病病理学中的作用

基本信息

批准号：
11670650
负责人：
YAMADA Tatsuo
金额：
$ 2.3万
依托单位：
Fukuoka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670650/
关键词：
Hepatocyte growth factor astrocyte Alzheimer disease ELISA

项目摘要

Hepatocyte growth factor (HGF) activator (HGFA) has been identified as a key enzyme that regulates the activity of HGF in vivo. Two types of HGFA inhibitor, type 1 (HAI-1) and type 2 (HAI-2), have been purified as potent inhibitors of HGFA.Our previous studies have shown that white matter astrocytes produce HGF, HGFA and HAI-1. We examined HAI-2 immunolabelling in the brains of neurologically normal persons and patients with Alzheimer's disease (AD). Furthermore, we identified the expression of the mRNA for HAI-2 by in situ hybridization histochemistry. The HAI-2 antibody stained astrocytes in all brain tissues. Expression of the mRNA for HAI-2 was also seen in astocytes. The intensities of the HAI-2 immunoreactivity and the signal for HAI-2 mRNA were similar in AD and normal control brains. These results suggest that almost all the astrocytes produce HAI-2. This is different from HAI-1 which appears to be produced only by white matter astrocytes.We also examined the level of HGF in cerebrospinal fluid (CSF) from AD and age matched disease control patients by a newly developed enzyme-linked immunoabsorbent assay system. Consistent with the immunohistochemical data, a significantly higher concentration of HGF in AD CSF was found as compared with controls. In both groups, a significant correlation was seen between CSF HGF levels and white matter high-signal foci detemined on brain MRI.These results suggest that CSF HGF levels could reflect the white matter damage.

肝细胞生长因子（HGF）活化剂（HGFA）已被确定为调节体内HGF活性的关键酶。两种类型的HGFA抑制剂1型（HAI-1）和2型（HAI-2）已被纯化为HGFA的有效抑制剂。我们以前的研究表明，白质星形胶质细胞产生HGF，HGFA和HAI-1。我们检查了HAI-2在神经系统正常人和阿尔茨海默氏病（AD）患者的大脑中的免疫标记。此外，我们通过原位杂交组织化学确定了HAI-2的mRNA的表达。 HAI-2抗体在所有脑组织中染色的星形胶质细胞。在astocytes中也可以看到mRNA对HAI-2的表达。 HAI-2免疫反应性的强度和HAI-2 mRNA的信号在AD和正常对照大脑中相似。这些结果表明，几乎所有星形胶质细胞都会产生HAI-2。这与HAI-1不同，HAI-1似乎仅由白质星形胶质细胞产生。我们还检查了通过新开发的酶链接的免疫ABSORBENT ASSAY ASSAY系统的AD和年龄相匹配的疾病控制患者的脑脊液（CSF）水平。与免疫组织化学数据一致，与对照组相比，发现AD CSF中的HGF浓度明显更高。在这两组中，CSF HGF水平与对大脑MRI的高信号焦点之间的显着相关性。这些结果表明CSF HGF水平可能反映了白质损害。