beta-cell neogenesis induced by adenovirus-mediated gene delivery of transcription factor pdx-1 into mouse pancreas.
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.
Taniguchi
H
H
Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, Osaka, Japan.
Yamato
E
E
Tashiro
F
F
Ikegami
H
H
Ogihara
T
T
Miyazaki
J
J
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002455:Cell Division; D003135:Common Bile Duct / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000628:therapy*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D018398:Homeodomain Proteins; D007150:Immunohistochemistry; D007267:Injections; D007515:Islets of Langerhans / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D014161:Transduction, Genetic / Q000379:methods
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; C407737:Neurog3 protein, mouse; C084010:pancreatic and duodenal homeobox 1 protein