Open Accessβ-cell neogenesis induced by adenovirus-mediated gene delivery of transcription factor pdx-1 into mouse pancreas
Author(s) -
H Taniguchi,
Eiji Yamato,
Fumi Tashiro,
Hiromasa Ikegami,
Toshio Ogihara,
Junichi Miyazaki
Publication year - 2003
Publication title -
gene therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.332
H-Index - 159
eISSN - 1476-5462
pISSN - 0969-7128
DOI - 10.1038/sj.gt.3301846
Subject(s) - neogenesis , biology , pancreas , ectopic expression , genetic enhancement , cancer research , pax4 , enteroendocrine cell , transcription factor , ductal cells , microbiology and biotechnology , gene delivery , viral vector , endocrine system , endocrinology , gene , diabetes mellitus , homeobox , genetics , islet , recombinant dna , hormone
beta-cell neogenesis is expected to provide a new therapy for diabetes. Numerous studies have demonstrated that transcriptional regulation involving pdx-1 is essential for endocrine neogenesis in vivo and in vitro. Therefore, it is possible that ectopic expression of pdx-1 in the pancreas could induce endocrine neogenesis. To test this possibility, we performed safe and efficient gene delivery of the pdx-1 gene into the mouse pancreas through the common bile duct using adenoviral vectors, and examined the effects of the ectopic expression of pdx-1. Here we show that adenovirus-mediated expression of pdx-1 can activate the endogenous pdx-1 gene, leading to beta-cell neogenesis and ductal proliferation. This technique is similar to the endoscopic retrograde cholangiopancreatography, which has been already established as a safe procedure for humans. Thus, beta-cell neogenesis induced by adenovirus-mediated expression of pdx-1 provides a novel strategy for gene therapy for a cure for diabetes mellitus.