Mechanisms of ulcerative colitis focusing on mucosal barrier disorder caused by bacteria possessed flagella
| Project/Area Number |
18K06019
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 42030:Animal life science-related
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| Research Institution | Shinshu University |
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Principal Investigator |
Yamanaka Hitoki 信州大学, 学術研究院総合人間科学系, 准教授 (30533921)
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| Co-Investigator(Kenkyū-buntansha) |
増山 律子 立命館大学, 食マネジメント学部, 教授 (60297596)
大沢 一貴 長崎大学, 先導生命科学研究支援センター, 教授 (90244756)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | ヘリコバクター属菌 / 盲結腸粘膜 / 腸内細菌叢 / 粘膜バリア / 抗菌ペプチド / マウス / 盲大腸粘膜 / ゲノム解析 / 大腸粘膜 / ゲノム配列 / 炎症 |
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| Outline of Final Research Achievements |
Helicobacter japonicus (Hj), which colonizes in lower intestinal tract of mice and has flagella, induces severe inflammation in the intestinal mucosa of SCID mice lucking functional B and T cells. In BALB/c mice, Hj infection enhances the expression of various cytokines and inducing mild inflammation in mucosa. In addition, Hj controls the expression of antimicrobial factors such as MUC2 and LYPD8 to create the environment in which they could colonize in intestine of mice. Hj infection also enhances the expression of Reg3β, Reg3γ and βdefensin14 resulting in the dysbiosis such as an increase in Bacteroides and a decrease in Clostridium XIVa and IV. Increased expression of these antimicrobial peptides maintained for a long period after infection. Our study shows that Hj infection induces dysbiosis resulting in causing mild inflammation persistently in intestinal mucosa
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| Academic Significance and Societal Importance of the Research Achievements |
Helicobacter属菌は、ピロリ菌以外では病原性やそのメカニズムが明らかではなく、また、人獣共通感染症と認識される菌も多い。本研究では、我々が実験用マウスから分離したHelicobacter japonicusに着目し、その病原性と共に一部ではあるがそのメカニズムについて明らかにすることができた。一方で、この細菌の感染による炎症誘導等の負の影響の他に、宿主粘膜バリアシステムの向上への貢献についても考えられ、この菌による宿主への影響で新たな視点が得られた。更に、本研究では、抗菌ペプチド発現評価系であるオルガノイドの作出法についても目途が立ち、今後の研究に応用が期待できる。
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Report
(4 results)
Research Products
(12 results)
