| Project/Area Number |
17390019
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
ITOH Nobuyuki Kyoto University, Graduate School of Pharmaceutical Sciences, Professor, 薬学研究科, 教授 (10110610)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAKE Ayumi Kyoto University, Graduate School of Pharmaceutical Sciences, Lecturer, 薬学研究科, 講師 (40346044)
KONISHI Morichika Kyoto University, Graduate School of Pharmaceutical Sciences, Assistant Professor, 薬学研究科, 助手 (00322165)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2006: ¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 2005: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | FGF / bone / cartilage / development / gene / lung / 骨・軟骨形成 / 細胞増殖 / 肺胞形成 / 細胞分化 |
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| Research Abstract |
Fgf18 is abundantly expressed in mouse embryonic lungs. To elucidate the roles of Fgf18 in mouse embryonic lung development, we examined the Fgf18-/- embryonic lungs. Although the sizes of the Fgf18-/- lungs were a little smaller in appearance than those of wild-type lungs, neither proximal nor distal airway branching in the Fgf18-/- lungs was impaired. However, the Fgf18-/- lungs at E18.5 had reduced alveolar space, thicker interstitial mesenchymal compartments, and many embedded capillaries. Cell proliferation in the Fgf18-/- lungs was also transiently reduced around E17. 5, although the expression of marker genes for lung epithelial cells in the Fgf18-/- lungs was not impaired. The present findings indicate that the Fgf18 plays roles in lung alveolar development during late embryonic lung development stages. The cell proliferation during the terminal saccular stage stimulated by Fgf18 might play roles in the remodeling of the distal lung.
Fgf18 was reported to negatively regulate the
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cell proliferation and differentiation of chondrocytes through the activation of Fgfr3c by analyzing Fgf18-/- mice at late embryonic stages. However, a contrary finding that Fgf signaling positively regulated the differentiation was also reported. Therefore, we reexamined the role of Fgf18 in the chondrocyte differentiation by analyzing the Fgf18-/- cartilaginous primordium at earlier embryonic stages. The expression profiles of ColX and Opn, markers of hypertrophic and terminal differentiated hypertrophic chondrocytes, respectively, indicate that the chondrocyte differentiation was significantly retarded in the Fgf18-/- primordium. In addition, Fgf18 protein positively regulates the differentiation of hypertrophic chondrocytes into terminal differentiated hypertrophic chondrocytes in the cultured Fgf18-/- primordium. Hypertrophic and terminal differentiated hypertrophic chondrocytes preferentially expressed Fgfr1c. The present results suggest that Fgf18 as a physiological ligand positively regulates the chondrocyte differentiation into terminal differentiated hypertrophic chondrocytes through the activation of Fgfr1c. Less
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