2021 Fiscal Year Final Research Report
Involvement of heme metabolic disorders in hepatocytes in the development of nonalcoholic steatohepatitis.
| Project/Area Number |
19K07203
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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 47060:Clinical pharmacy-related
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| Research Institution | Teikyo Heisei University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
水間 俊 帝京平成大学, 薬学部, 教授 (80229715)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 非アルコール性脂肪性肝炎 / NASH / HO-1 / ヘム |
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| Outline of Final Research Achievements |
It has been suggested that abnormal iron metabolism is associated with the development and progression of non-alcoholic steatohepatitis (NASH), but the mechanism of this association remains unclear. In this study, we focused on the heme biosynthesis pathway, one of the iron utilization pathways in hepatocytes, as a factor linking the onset and progression of NASH and abnormal iron metabolism, and examined the relationship between heme biosynthesis pathway and NASH. The results suggest that the heme biosynthesis pathway in hepatocytes is impaired under methionine and choline deficiency conditions, which is one of the methods used to create animal models of NASH. We also found that an inducer of HO-1, a heme degrading enzyme, reduced the cytotoxicity of tamoxifen, one of the causative agents of NASH.
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| Free Research Field |
医療薬学
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| Academic Significance and Societal Importance of the Research Achievements |
NASHはメタボリックシンドロームの肝での表現型として増加傾向を示し、肝疾患領域における重要性が増している。一方で発症・進展の機序は依然不明であり、その治療法も確立されていない。本研究は細胞内のヘム生合成経路とのリンクというNASHの病態の新たな側面を提示し、NASHの予防、治療応用への理論基盤の発展に貢献することが期待できる。
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