| Co-Investigator(Kenkyū-buntansha) |
ISHIWATA Toshiyuki Nippon Medical School, Medicine, Associate Professor, 医学部, 助教授 (90203041)
NAITO Zenya Nippon Medical School, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (20237184)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
Keratinocyte growth factor, KGF, is a member of FGF families that has been known to participate in regulation of cell growth, differentiation, adhesion, migration and the tissue morphogenesis. Furthermore, it is reported that FGF and the receptor FGFR contribute to the development of the pancreas. The specific receptor of KGF, KGFR/FGFR2-IIIb, is also suggested to be an important molecule in the early period of pancreatic development. We, having focused on the expression of KGF and KGFR/FGFR2-IIIb, applied both the pancreatectomy model and the acute L-arginine-pancreatitis model of the rat to scrutinize regeneration of the adult pancreas. We tried further to identify the pancreatic progenitor cells that contribute to regenerate endocrine and exocrine cells.
A. Rat pancreatectomy model
1) Many Ki67 positive cells were observed in pancreatic acinar cells, excretory ductal cells and endocrine cells of the islet. The number of Ki67 positive cells increased significantly in 3 days after pancr
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eatectomy and decreased gradually in seven days after the pancreatectomy. 2) The PDX-1 positive cells also were observed in significantly large numbers in pancreatectomy group in comparison with control group. This suggests that expression of PDX-1 increases after pancreatectomy. 3) KGFR was expressed in α-cells of the pancreatic islets implying that KGF contributes to the functional differentiation of the α-cells.
B. L-arginine-induced pancreatitis
1) Six hours after L-arginine injection, interstitial edema was observed in the pancreas, whereas on day 4 postinjection, there was severe pancreatic necrosis. 2) Neovascularization and ductal-ductular proliferation were also present in the pancreas. 3) Immunohistochemical analysis revealed increased Ki-67 labeling in acinar cells and capillary endothelial cells. 4) Immunoblotting using anti-nestin antibody revealed increased nestin expression after L-arginine injection. In the control rat pancreas, nestin immunoreactivity was detected in a few capillary endothelial cells in some islets. 5) After L-arginine injection, nestin was expressed in proliferating capillary endothelial cells, in stellate cells surrounding ductular structures and in submesothelial cells. Conclusions : Transient nestin expression occurs in specific cell types during the proliferative stage after recovery from L-arginine-induced pancreatitis and may represent the contribution of stem cells and/or progenitor cells to the regenerative capacity of the pancreas. Less
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