2023 Fiscal Year Final Research Report
Antioxidative nanoparticles attenuate the development of steatohepatitis and inhibit hepatocarcinogenesis in mice induced by lipopolysaccharide from periodontal bacteria.
| Project/Area Number |
21K11668
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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 59040:Nutrition science and health science-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
鈴木 英雄 筑波大学, プレシジョン・メディスン開発研究センター, 客員教授 (00400672)
内田 文彦 筑波大学, 医学医療系, 講師 (70736008)
岡田 浩介 筑波大学, 医学医療系, 准教授 (80757526)
正田 純一 筑波大学, 医学医療系, 客員教授 (90241827)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | NASH / 歯周病菌 / Oral-Gut-Liver axis / Nrf2 / 遺伝子改変マウス |
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| Outline of Final Research Achievements |
Lipopolysaccharide (LPS) derived from periodontal bacteria reportedly contributes to the development of non-alcoholic steatohepatitis (NASH). The transcription factor Nrf2 plays a role of phagocytosis function against LPS. Macrophage-specific Nrf2 gene rescue mice (Nrf2-mRes), which express Nrf2 only in macrophages, was generated in our laboratory. Nrf2-KO mice developed severe steatohepatitis with liver inflammation and fibrosis compared with WT mice, and steatohepatitis was ameliorated in Nrf2-mRes mice. The results suggested that Nrf2 is an important inhibitory factor against steatohepatitis. Following the observation, at present, we have started a study to clarify the protective mechanisms by which the oral administration of one of the nanoparticle-type antioxidants, RNPO attenuates NASH development through the oral-gut-liver axis axis in the mice.
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| Free Research Field |
健康応用科学
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| Academic Significance and Societal Importance of the Research Achievements |
高齢者における歯周病の有病率は高率であり，そのLPSの血中濃度は年齢の高齢化ともに増加する．NASHと肝発癌を誘導する歯周病細菌の役割において, LPSがそれらのプロモーションをきたすことが推測されている．本研究では，Kupffer細胞のみにNrf2を発現するNrf2遺伝子レスキューマウス(Nrf2-mRes)を作製した．Nrf2-mResでは，高脂肪食摂餌(HFD)とLPS投与によるNASH肝病変(肝炎症・線維化)の発症が抑止されることを解明した．Kupffer細胞Nrf2は重要なNASH防御因子と考えられた．本研究成果はNASH-肝癌予防に向けた新しい学術的成果として捉えることが出来る.
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