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

大疱性表皮松解症是由基底膜带结构蛋白编码基因突变引起的。特别是由III型胶原和层粘连蛋白5基因产生的亚型表现出严重的表型和低的生活质量。这些结构蛋白被认为是由表皮角质形成细胞产生的。许多皮肤科研究人员打算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种将III型胶原和层粘连蛋白5或它们的基因从真皮侧持续输送到基底膜区的系统。去年我们成功地纯化了大量的重组III型胶原。注射该蛋白可诱导基底膜区VII型胶原沉积。基因转导的成纤维细胞也能使II型胶原进入基底膜。此外，将这些成纤维细胞植入支架中增加了基底膜区的III型胶原的数量。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持续输送到基底膜区的系统的建立。

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.