| Project/Area Number |
16H05086
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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 | Chiba University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
平川 城太朗 千葉大学, 大学院薬学研究院, 助教 (30609160)
|
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| Research Collaborator |
Komatsu Masaaki
Katayama Takane
Kobayashi Motohiro
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | オートファジー / 腸内細菌 / 抗菌ペプチド / ムチン / 大腸炎 / 免疫学 |
|---|
| Outline of Final Research Achievements |
In this study, we found that colonic epithelium-specific autophagy-related gene Atg7-conditional knockout (cKO) mice showed exacerbated dextran sulfate sodium (DSS)-induced colitis compared with wild-type mice in relation to massive infiltration of bacteria into the colon. In the cKO mice, expression of specific antimicrobial peptides was significantly reduced, and marked changes in gut microbiota were observed. Furthermore, in cKO mice, the secretion of mucins that are involved in the protection of colonic mucus and inflammation was significantly reduced. These results suggest that autophagy of the colonic epithelium contributes to the regulation of normal intestinal bacterial balance and defense against inflammation via antimicrobial peptide and mucin production.
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| Academic Significance and Societal Importance of the Research Achievements |
大腸上皮細胞のオートファジーは、抗菌ペプチドの発現、正常な腸内細菌叢の維持、およびムチン分泌を維持することで、大腸炎の防御に寄与することが示唆された。今後は、オートファジーの欠損によって産生低下する抗菌ペプチドが作用する菌種の同定やその作用機序の解明等により、腸内細菌バランスの正常化に基づく炎症性腸疾患治療法開発の分子基盤が確立することが期待される。
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