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Establishment of a system in which type VII collagen and laminin 5 or their genes are continuously delivered from the dermal side to the basement membrane zone

建立将VII型胶原蛋白和层粘连蛋白5或其基因从真皮侧连续输送至基底膜区的系统

基本信息

批准号：
15390337
负责人：
SAWAMURA Daisuke
金额：
$ 9.41万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390337/
关键词：
epidermolysis bullosa dystrophic severe type VII collagen laminin 5 protein therapy gene transfer dermis

项目摘要

Epidermolysis bullosa is caused by mutations in the genes encoding structural proteins of basement membrane zone. Especially, the subtypes resulting from type VII collagen and laminin 5 genes showed severe phenotype and low quality of life. These structural proteins are thought to be produced by epidermal keratinocytes. Many dermatological investigators intend to introduce the causative genes to keratinocytes and to supply those gene products to basement membrane. The aim of this study was to establish a system in which type VII collagen and laminin 5 or their genes were continuously delivered from the dermal side to the basement membrane zone. We succeeded in purification of a large amount of recombinant type VII collagen last year. The injection of the protein induced deposition of type VII collagen in the basement membrane zone. Also injection of gene-transferred fibroblasts enabled type VII collagen to go into the basement membrane. Furthermore, implantation of these fibroblasts in scaffold increased the amount of type VII collagen in the basement membrane zone. Thus, we think that we can achieve establishment of the system in which type VII collagen and laminin 5 or their genes are continuously delivered from the dermal side to the basement membrane zone.

大疱性表皮病是由编码基底膜带结构蛋白的基因突变引起的。尤其是由VII型胶原和层粘连蛋白5基因引起的亚型表现出严重的表型和低生活质量。这些结构蛋白被认为是由表皮角质形成细胞产生的。许多皮肤病学研究者试图将致病基因导入角质形成细胞，并将这些基因产物提供给基底膜。本研究的目的是建立一个系统，在该系统中，VII型胶原和层粘连蛋白5或其基因从真皮侧连续递送到基底膜区。去年，我们成功地纯化了大量的重组VII型胶原蛋白。注射的蛋白质诱导沉积的VII型胶原在基底膜区。此外，注射基因转移的成纤维细胞使VII型胶原蛋白进入基底膜。此外，这些成纤维细胞在支架中的植入增加了基底膜区中的VII型胶原的量。因此，我们认为我们可以实现VII型胶原和层粘连蛋白5或它们的基因从真皮侧连续递送到基底膜区的系统的建立。