Metabolic regulation and the remodeling tissue microenvironment
| Project/Area Number |
18K07211
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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 50010:Tumor biology-related
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| Research Institution | Kindai University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
天野 恭志 近畿大学, 医学部, 助教 (20549331)
古室 暁義 近畿大学, 医学部, 講師 (50512274)
上田 健 近畿大学, 医学部, 准教授 (60585149)
太田 一成 近畿大学, 医学部, 助教 (70589928)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 組織微小環境 / がん / 代謝制御 / エピジェネティクス / マウスモデル / 代謝異常 / 代謝 |
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| Outline of Final Research Achievements |
Disruption of the proteostasis network leads to a variety of human diseases including neurodegenerative disorders, metabolic diseases, lysosome diseases, cancer and aging. In this project, we investigated Bat3 functions in vivo using original liver-specific Bat3 deficient mice with special emphasis on metabolic regulation. Histological, biochemical and molecular biological analyses showed that Bat3 deficiency in the liver resulted in liver damages and enhanced ER stress, metabolic stress and inflammation signature. These data suggest that Bat3 deficiency induced dysregulated proteostasis and metabolic stress, which exacerbate liver damage in vivo.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、生活習慣病に強く関連する非アルコール性脂肪肝炎が原因とされる慢性肝炎、肝硬変、肝がん症例が世界的に増加傾向にある。しかしながら、代謝ストレスにより惹起される肝障害、肝硬変、肝がんの個体レベルでの発症の詳細は不明な点も多い。我々の研究結果は、我々が独自に作成したマウスモデルが代謝ストレスにより引き起こされる肝炎、肝硬変、自然発症肝がんの病態を理解するための有用なモデルとなり得ること示唆している。従って、これらのモデルを用いて代謝性肝障害に関与するシグナル経路の詳細を検討することはその治療法、予防法を開発する上で社会的にも大変に意義深い。
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Report
(4 results)
Research Products
(37 results)
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[Journal Article] The KDM4B-CCAR-MED1 axis is a critical regulator of osteoblast differentiation and bone homeostasis2021
Author(s)
Kyunghwan Kim, Sun-Ju Yi, You-Jee Jang, Hye-Jung Kim, Kyubin Lee, Hyerim Lee, Yeojin Kim, Junil Kim, Seon Young Hwang, Hitoshi Okada, Jae-Il Park, Kyuho Kang, Jin Sook Song
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Journal Title
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Bat3 controls Tim-3 mediated T cell terminal differentiation and exhaustion in an mTORC2-dependent manner2021
Author(s)
Chen Zhu, Karen O. Dixon, Meromit Singer, Guangxiang Gu, Sheng Xiao, Sarah Zaghouani, Chao Wang, Markus A. Schramm, Kouichiro Goto, Elena Christian, Kathleen Newcomer, Manu Rangachari, Orit Rosenblatt-Rosen, Hitoshi Okada, Tak Mak, Aviv Regev, Vijay Kuchroo
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Journal Title
Science Advances
Volume: -
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition2020
Author(s)
Simone F. Glaser, Andreas W. Heum, Lukas Tombor, Patrick Hofmann, Marion Muhly-Reinholz, Ariane Fischer, Stefan Gunther, Karoline E. Kokot, Hitoshi Okada, David Hassel, Sandeep Kumar, Hanjoong Jo, Reinier A. Boon, Wesley Abplanalp, David John, Jes-Niels Boeckel, and Stefanie Dimmeler
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Journal Title
Proceedings of the National Academy of Sciences
Volume: 117
Issue: 15
Pages: 8657-8657
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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