| Project/Area Number |
21590805
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
SUZUKI Shinji 東京医科歯科大学, 大学院・医歯学総合研究科, 助教 (10456212)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Tetsuya 東京医科歯科大学, 大学院・医歯学総合研究科, 寄附講座教員 (70265809)
WATANABE Mamoru 東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (10175127)
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| Co-Investigator(Renkei-kenkyūsha) |
ARAKI Akihiro 東京医科歯科大学, 医学部附属病院, 講師 (80361690)
NAGAHORI Masakazu 東京医科歯科大学, 医学部附属病院, 助教 (60420254)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 大腸上皮幹細胞 / Wntシグナル / Notchシグナル/初代培養/細胞移植治療 / 大腸上皮細胞 / 細胞増殖 / 細胞分化 / Notchシグナル |
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| Research Abstract |
Wnt and Notch pathways are known to function together to regulate proliferation and differentiation of intestinal epithelium ; however, the molecular mechanism of their functional interplay remains unclear. In this study, we aimed at investigating the signaling crosstalk between these two pathways in colonic epithelium. First, by using several human colon cancer-derived cell lines, we have demonstrated that the expression of Hath1, a bHLH transcription factor known to be involved in Notch signaling, is regulated by the proteasome-mediated protein degradation that is under the control of Wnt signaling. We also showed that this post-translational regulation of Hath1 by Wnt/Notch signals is important for cell fate determination of colonic cells. Second, in order to investigate the crosstalk between Wnt/Notch signals, we have established a novel method to isolate and culture normal colonic epithelium in vitro. By this method, colonic cells continuously grow and the Lgr5+colonic stem cells preferentially expand as a result of Wnt/Notch activation. We also showed for the first time that the cultured colonic cells are able to regenerate damaged epithelium in recipient mice when transplanted. These data would built a basis for the future study to elucidate molecular mechanism that govern the interplay of Wnt/Notch signals to regulate the regenerative properties and/or malignant transformation of colonic epithelial cells.
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