| Project/Area Number |
19K17425
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Shuji Hibiya 東京医科歯科大学, 医学部附属病院, 特任助教 (20801963)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 炎症塑性 / 炎症性腸疾患 / 腸管上皮幹細胞 / 長期炎症 |
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| Outline of Research at the Start |
炎症性腸疾患は、長期炎症で不可逆的に機能不全に陥った上皮細胞塑性こそ病態の根幹であると着想し、塑性獲得機構及びリセット機構の解明がIBD病態解明や治療法開発に直結すると着想した。本研究では、独自に構築したマウス腸管体外長期炎症モデルをヒト体外長期炎症モデルにまで発展させ、ヒト腸管上皮幹細胞における長期炎症下での塑性獲得機構及び塑性リセット機構を解析する。本研究で得られる成果はIBDの上皮細胞病態解明及び完治を目指した治療法の基盤構築に繋がるものである。
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| Outline of Final Research Achievements |
The characteristic of inflammatory bowel disease (IBD) represented by ulcerative colitis and Crohn's disease is that relapse is repeated. Although inflammatory cell infiltration is not observed in the pathology after IBD remission, epithelial cell dysfunction such as crypt distortion and goblet cell depletion is observed, which suggests that it cannot be recovered by long-term inflammation. In this study, we have succeeded in delineating differences due to inflammation but not individual differences by comparing the same human cells before and after long-term inflammation. We identified an irreversible factor due to long-term inflammation and showed that targeting that factor restores some traits.
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| Academic Significance and Societal Importance of the Research Achievements |
長期炎症による非可逆機構を初めて明らかとした。非可逆因子を標的とすることで、炎症塑性の一部可塑性変化を認め上形質の改善を認めたことから、再燃予防を見据えた新規炎症性腸疾患の治療薬開発が期待される。
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