Elucidation of the role of hematopoietic cells in the development and progression of liver cirrhosis due to NASH and establishment of new therapeutic targets.
| Project/Area Number |
19K17404
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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 | University of Miyazaki |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | NASH / 肝硬変 / fibrocyte / CDAHFD / CD11b-DTR / fibroycyte / clodronate liposome / TET2 / 非アルコール性脂肪肝炎 |
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| Outline of Research at the Start |
本研究では、血液細胞が肝線維化の進展や脂肪肝の発症に与える影響を明らかにし、肝硬変やNASHの新たな治療の標的になり得るかを明らかにする。1つ目に単球由来の細胞であるfibrocyteの肝線維化における役割を明らかにし、fibrocyteを標的とした治療モデルを作成する。2つ目にTET2の機能欠損が、脂肪肝、NASHの病態に影響を与えるかを検討し、血液細胞と脂肪肝の関連性を検討する。
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| Outline of Final Research Achievements |
Carbon tetrachloride (CCl4: carbon tetrachloride)-induced liver fibrosis model mice were treated with clodronate liposomes (CL: clodronate liposome) to selectively eliminate monocytes. Although fibrocytes in the liver were reduced compared to the non-CL-treated group, the progression of liver fibrosis was not suppressed. Therefore, the contribution of fibrocyte to liver fibrosis in the CCl4-induced liver fibrosis model is considered to be small. In the future, we plan to examine whether the elimination of monocytes in the liver of NASH model mice also reduces fibrocyte in the liver and suppresses the progression of liver fibrosis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、CCl4誘導肝線維化モデルにおいては、その線維化進展における単球由来fibrocyteの寄与は小さいものと考えられ、その線維化改善のためにはfibrocyte以外の細胞を治療標的とするのが妥当であると考えられた。ただし、NASHモデルに関しては、その線維化進展におけるfibrocyteの寄与の程度は解明されていないため、今後の追加研究が必要と考えられる。
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Report
(4 results)
Research Products
(2 results)
