Pancreas · 2005
Regenerative and therapeutic effects of heparin-binding epidermal growth factor-like growth factor on diabetes by gene transduction through retrograde pancreatic duct injection of adenovirus vector.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Kozawa Junji, Tokui Yae, Moriwaki Makoto, Li Ming, Ohmoto Hiroshi, Yuan Ming, Zhang Jun, Iwahashi Hiromi, Imagawa Akihisa, Yamagata Kazuya, Tochino Yoshihiro, Shimomura Iichiro, Higashiyama Shigeki, Miyagawa Jun-ichiro
Аннотация
OBJECTIVES: In the adult pancreas, pre-existing beta cells, stem cells, and endocrine progenitor cells residing in the duct lining are considered important sources for beta-cell regeneration. A member of the epidermal growth factor (EGF) family, heparin binding (HB)-EGF, may promote this process. We examined whether HB-EGF gene transduction into duct cells could promote beta-cell regeneration.
METHODS: We administered an HB-EGF adenovirus vector construct to male Institute of Cancer Research mice by retrograde injection through the pancreatic duct. We also performed HB-EGF gene transduction into cultured duct cells.
RESULTS: On immunohistochemical and histomorphometric analysis of the experimental group, insulin-positive cells differentiated from duct cells, and the 5-bromo-2-deoxyuridine labeling index of beta cells was significantly increased. beta-cell mass was also increased, and the glucose tolerance of diabetic mice was improved at 12 weeks after injection. Using cultured pancreatic duct cells, we confirmed that HB-EGF gene transduction induced both insulin gene expression and insulin production by these cells.
CONCLUSIONS: These results indicate that HB-EGF gene transduction into adult pancreatic duct cells not only promotes the proliferation of pre-existing beta cells but also leads to beta-cell differentiation from duct cells, and the resulting increase in beta-cell mass improves glucose tolerance.
METHODS: We administered an HB-EGF adenovirus vector construct to male Institute of Cancer Research mice by retrograde injection through the pancreatic duct. We also performed HB-EGF gene transduction into cultured duct cells.
RESULTS: On immunohistochemical and histomorphometric analysis of the experimental group, insulin-positive cells differentiated from duct cells, and the 5-bromo-2-deoxyuridine labeling index of beta cells was significantly increased. beta-cell mass was also increased, and the glucose tolerance of diabetic mice was improved at 12 weeks after injection. Using cultured pancreatic duct cells, we confirmed that HB-EGF gene transduction induced both insulin gene expression and insulin production by these cells.
CONCLUSIONS: These results indicate that HB-EGF gene transduction into adult pancreatic duct cells not only promotes the proliferation of pre-existing beta cells but also leads to beta-cell differentiation from duct cells, and the resulting increase in beta-cell mass improves glucose tolerance.
Предметные рубрики MeSH
AdenoviridaeAnimalsBody WeightBromodeoxyuridineCells, CulturedDiabetes Mellitus, ExperimentalEpidermal Growth FactorGenetic TherapyGlucose Tolerance TestHeparin-binding EGF-like Growth FactorHomeodomain ProteinsImmunohistochemistryInjectionsIntercellular Signaling Peptides and ProteinsIslets of LangerhansMaleMiceMice, Inbred ICRPancreatic DuctsRegenerationReverse Transcriptase Polymerase Chain ReactionTrans-Activators