2018 Fiscal Year Final Research Report
Elucidation of the molecular mechanisms of human non-alcoholic steatohepatitis (NASH)
| Project/Area Number |
16K01850
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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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| Research Field |
Applied health science
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| Research Institution | National Center for Global Health and Medicine |
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Principal Investigator |
Yasuda Kazuki 国立研究開発法人国立国際医療研究センター, その他部局等, その他 (80311611)
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| Research Collaborator |
Nammo Takao
Funahashi Nobuaki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | NASH / 生活習慣病 / mRNA / 遺伝子発現調節 / クラスター |
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| Outline of Final Research Achievements |
We performed comprehensive analysis of transcriptome of the liver obtained from Japanese NASH (non-alcoholic steatohepatitis) subjects.
Unsupervised two-way cluster analyses revealed that genes with similar function, such as inflammation, lipid metabolism, cell profanation or fibrosis, constituted co-regulated gene clusters, which were quite compatible with “multiple parallel hits hypothesis” of NASH development. We analyzed mechanisms of transcriptional regulation of two interesting genes, AKR1B10 and a novel member of the same family AKR1B15, using human HuH7 cells, and found specific upstream signals for each gene, suggesting complex pathophysiology of NASH.
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| Free Research Field |
生活習慣病、内分泌・代謝学
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| Academic Significance and Societal Importance of the Research Achievements |
NASHは極めて頻度の高い疾患であるだけでなく、肝がんの発生母地として、また心血管病変のハイリスクとして重要であるが、病態の多くが不明で、侵襲的な肝生検以外に確定した診断方法がなく、さらに有効な治療薬もないなど、unmet medical needsの代表的疾患である。本研究は実際のヒト組織を用いてNASHの分子病態を明らかにし、画期的な診断・治療薬の開発への道を開く可能性を秘めた研究である。
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