2020 Fiscal Year Final Research Report
Development of therapeutic drug for steatohepatitis by liver-specific bio-nanocapsules equipped with RNAi targeting TTC39B
| Project/Area Number |
18H03532
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 90120:Biomaterials-related
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
黒田 俊一 大阪大学, 産業科学研究所, 教授 (60263406)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 脂肪肝炎 / バイオナノカプセル / TTC39B / PCSK9 / コレステロール |
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| Outline of Final Research Achievements |
We developed a new steatohepatitis model by focusing on, a dietary oxidized cholesterol, 7-ketocholesterol (7KC). Administration of 7KC resulted in decrease in mitochondrial activity, modulation of autophagy mechanism, expression of inflammatory cytokines in obesity/diabetes model mice. Then, we reported that 7KC exacerbated lipid accumulation, inflammatory cell infiltration, and liver fibrosis (Frontier in Endocrinology 2020). In addition, we also succeeded in creating a “steatohepatitis-related cardiomyopathy” in a rodent NSH model (in submission). This is the first model showing NLRP3 inflammasome activation and cardiac dysfunction due to cholesterol accumulation in both the liver and heart.
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| Free Research Field |
脂質代謝
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で開発したモデルはこれまでの脂肪肝炎モデルに比し、肝線維化の進行が早く、これまでのメチオニン・コリン欠乏食（MCD）による脂肪肝炎と比較して、よりヒトの脂肪肝炎の組織像に近い所見がえられており、今後の核酸医薬の試験に有用であると考えられる。
RNAi搭載バイオナノカプセルは、均質な粒子径を売るための条件検討がほぼ完了した。
より迅速な、核酸医薬搭載バイオナノカプセルの効果判定試験が可能となった。
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