2023 Fiscal Year Final Research Report
The role of p62 in the development of NASH and hepatocellular carcinoma – approach from both basic and clinical medicine
| Project/Area Number |
21H03010
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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 55020:Digestive surgery-related
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
徳重 克年 東京女子医科大学, 医学部, 教授 (60188729)
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 | p62/Sqstm1 / NASH / 肝癌 / autophagy |
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| Outline of Final Research Achievements |
The aim of this research is to elucidate the mechanisms of development of NASH and hepatocellular carcinoma from both basic and clinical medicine. The hepatocytes, adipocytes, or macrophages specific conditional p62 knock-in (rescued) mice were product and analyzed in NASH development. The hepatocyte specific p62 knock-in mice were suppressed the development of NASH with severe hepatic inflammation and fibrosis compared with other p62 gene modified-mice despite their similar obese. Moreover, p62 immunohistochemical analyses using clinical liver specimens from 50 hepatocellular carcinoma developed from NASH, 49 HCCs developed from chronic viral hepatitis C, and 48 liver metastases of colorectal cancer from both tumorous and non-tumorous areas which were collected by hepatic resection surgery showed that p62 immunohistochemical expression and pattern was correlated with liver inflammation and fibrosis.
p62 of hepatocytes could be a new target for NASH treatment.
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| Free Research Field |
消化器外科学
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| Academic Significance and Societal Importance of the Research Achievements |
非アルコール性脂肪性肝炎（NASH）の進行および肝癌発生を阻止するための薬物治療は確立していない．本研究は，肝細胞のp62がNASHの防御に重要であること，ヒトでもNASH進展に関連することを示した．これらの結果は，特に肝細胞のp62の発現が肝脂肪化のみならず肝炎症線維化をもコントロールし得る可能性と，p62が新しいNASHの治療標的と成り得る可能性を示した．NASHの今後の薬物治療開発のうえで，本研究の意義は大きいと考えられる．
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