| Project/Area Number |
19K16477
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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 48010:Anatomy-related
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| Research Institution | University of Miyazaki |
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Principal Investigator |
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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 | estrogen / epigenetics / colitis / Epigenetics / Estrogen receptor / GPR30 / IBD / Colitis / 解剖学 / 組織細胞化学 |
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| Outline of Research at the Start |
In this research we will be elucidated ERβ-mediated estrogen role in epigenetic regulation on epithelial barrier function and also we will investigate the effect of epigenetic treatment in IBD. Moreover, we will study gender and age-dependent expression of ERβ in intestine and ERβ-mediated transcriptional activity in colon. Direct involvement of ERβ in epigenetic regulation will be examined in ERβKO and also ERβ knock-down mouse colon. The epigenetic changes in the ERβKO will be the key points to explain the ERβ-mediated estrogen role in mouse model of IBD.
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| Outline of Final Research Achievements |
The results of this study suggest that estrogen has protective effect in colitis through its receptor ERβ and GPR30. Estrogen signaling acts through both genomic and non-genomic pathways. Moreover, epigenetic regulator HDAC, suberoylanilide hydroxamic acid attenuates inflammatory changes in DSS-induced colitis by suppressing local secretion of pro-inflammatory cytokines and chemokines and also by suppressing mobilization and accumulation of inflammatory cells. Detailed epigenetic analysis was detected that H3K36 expression was associated with colonic inflammation.
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| Academic Significance and Societal Importance of the Research Achievements |
Estrogen targeted epigenetic therapy will help to develop new treatment approach for inflammatory bowel disease. Our results clearly indicated that estrogen has protective effect through its receptor GPR30 in mouse colitis model.
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