权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

An attempt to gene therapy for renal disease using adenovirus vector

利用腺病毒载体进行肾病基因治疗的尝试

基本信息

批准号：
06671128
负责人：
KATOH Tetsuo
金额：
$ 0.38万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671128/
关键词：
gene therapy adenovirus hepatocyte growth factor kidney メサンギウム細胞

项目摘要

The present research project was designed to examined the availability of adenovirus vector for gene therapy for renal disease.The data obtained during 1995-1996 is described below : 1.The preparation of adnovirus vector. We made the adenovirus vector containing the coding region of rat hepatocyte growth factor (HGF) in collaboration with Dr H.Hamada of Cancer Institute. 2.The application of adenovirus vector into the rat. In attempts to develop the method for the efficient application to the rat, we tried to apply the vector through intra-arterial, direct, intra-benous, and intra-urethreal approach. 3.Detection of gene expression. To detect the genes which adenovirus vector encode, Northern blot analysis or immunohistochemical staining method was used 2-8 weeks after the gene transfer. With these method, the amount of gene expression was not sufficient for the practical level required for gene therapy, which results were in accordance with reports from other institutes. These findings … More suggest that adenovirus vector has some limitation for the clinical use for gene therapy. 4.Clinical investigation. We measured the plasma level of HGF to evaluate the clinical implication of HGF in the development of chronic renal failure. The result indicate that plasma HGF level was increased in patients of end stage renal disease, suggesting that HGF might act as an endogenously produced renal protecting factor. Plasma HGF level was also increased in renal transplantation recipients, of which clinical implication should be investigated further. 5.Molecular mechanism for the development of chronic renal failure. To elucidate the molecular basis for the development of chronic renal failure, vascular smoothe muscle cells and mesangial cells were cultured on flexible bottome dish, on which cell were constantly exposed to cyclic stretch/relaxation. These cells expressed PHTrP or TGF-b mRNA in response to stretch, which implys a role of glomerular hypertension in the development glomerular sclerosis. Less

本研究计划旨在检验腺病毒载体在肾脏疾病基因治疗中的可用性。1995-1996年期间获得的数据说明如下：腺病毒载体的制备。我们与美国癌症研究所的H.Hamada博士合作制备了含有大鼠肝细胞生长因子（HGF）编码区的腺病毒载体。腺病毒载体在大鼠体内的应用。为了开发有效应用于大鼠的方法，我们尝试通过动脉、直接、静脉和尿道内途径应用载体。3.基因表达检测。转染后2 ~ 8周采用Northern blot法或免疫组织化学染色法检测腺病毒载体编码的基因。这些方法的基因表达量不足以满足基因治疗所需的实际水平，这与其他研究所的报告结果一致。这些发现提示腺病毒载体在临床应用于基因治疗方面存在一定的局限性。4.临床调查。我们测量血浆HGF水平，以评估HGF在慢性肾衰竭发展中的临床意义。结果提示终末期肾病患者血浆HGF水平升高，提示HGF可能是一种内源性肾保护因子。肾移植受者血浆HGF水平升高，其临床意义有待进一步研究。5.慢性肾衰竭发生的分子机制。为了阐明慢性肾功能衰竭发生的分子基础，我们在柔性底皿上培养血管平滑肌细胞和系膜细胞，使细胞不断处于循环拉伸/松弛状态。这些细胞在拉伸反应中表达PHTrP或TGF-b mRNA，这暗示肾小球高血压在肾小球硬化的发展中起作用。少