Endoplasmic reticulum stress, Mallory-Denk body and autophagy in fatty liver disease
| Project/Area Number |
18K07988
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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 53010:Gastroenterology-related
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
Harada Masaru 産業医科大学, 医学部, 教授 (00241175)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 脂肪性肝疾患 / 銅 / C型肝炎 / ウイルソン病 / 小胞体ストレス / Mallory-Denk体 / オートファジー / 酸化ストレス / 非アルコール性脂肪性肝疾患 |
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| Outline of Final Research Achievements |
I examined the effects of endoplasmic reticulum (ER) stress inducers including free fatty acids on hepatocyte-derived cell lines. Saturated fatty acid, proteasome inhibitors, copper and hepatitis C virus induced oxidative stress and ER stress. They also inhibited autophagic flux. Inhibition of autophagic flux seemed to be associated with cell injury, Mallory-Denk body-like intracellular inclusion formation and DNA injury. Unsaturated fatty acids and zinc improved oxidative stress, ER stress, autophagic derangement, Mallory-Denk body-like inclusion formation, DNA injury and cell damage. Therefore, unsaturated fatty acids and zinc must be useful for the treatment of oxidative stress and ER stress associated liver diseases, such as fatty liver diseases, diabetes-related liver disease, alcohol-associated/related disease, Wilson diseases and hepatitis C virus infection.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、脂肪性肝疾患、アルコール関連肝疾患や2型糖尿病等による肝細胞癌が増加している。C型肝炎の治療も進歩したが、肝炎ウイルス排除後の肝細胞癌も多く存在する。これらの疾患に関連する重要なことは小胞体ストレスである。本研究ではこれらの病態にオートファジーの後期段階の障害や肝細胞内封入体の形成が関与していることを明らかとした。さらに小胞体ストレス、オートファジー障害と封入体形成の改善に不飽和脂肪酸や亜鉛の投与が利用可能なことを明らかとした。このことは多くの肝疾患の進展防止に不飽和脂肪酸と亜鉛が有用であることを明らかにしたと考える。
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Report
(4 results)
Research Products
(30 results)
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[Journal Article] Role of HO-1 against Saturated Fatty Acid-Induced Oxidative Stress in Hepatocytes2021
Author(s)
Ogino N, Miyagawa K, Nagaoka K, Matsuura-Harada Y, Ogino S, Kusanaga M, Oe S, Honma Y, Harada M, Eitoku M, Suganuma N, Ogino K
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Journal Title
Nutrients
Volume: 13
Issue: 3
Pages: 993-993
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Idiopathic copper toxicosis: is abnormal copper metabolism a primary cause of this disease?2020
Author(s)
Harada M, Honma Y, Yoshizumi T, Kumamoto K, Oe S, Harada N, Tanimoto A, Yabuki K, Karasuyama T, Yoneda A, Shibata M.
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Journal Title
Med Mol Morphol.
Volume: 53
Issue: 1
Pages: 50-55
DOI
Related Report
Peer Reviewed
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[Journal Article] Predictors of hepatocellular carcinoma recurrence associated with the use of direct-acting antiviral agent therapy for hepatitis C virus after curative treatment: A prospective multicenter cohort study.2019
Author(s)
Nakano M, Koga H, Ide T, Kuromatsu R, Hashimoto S, Yatsuhashi H, Seike M, Higuchi N, Nakamuta M, Shakado S, Sakisaka S, Miuma S, Nakao K, Yoshimaru Y, Sasaki Y, Oeda S, Eguchi Y, Honma Y, Harada M, Nagata K, Mawatari S, Ido A, Maeshiro T, Matsumoto S, Takami Y, Sohda T, Torimura T
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Journal Title
Cancer Med.
Volume: 印刷中
Issue: 5
Pages: 2646-2653
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Direct-acting antiviral agents do not increase the incidence of hepatocellular carcinoma development: a prospective, multicenter study2019
Author(s)
Ide T, Koga H, Nakano M, Hashimoto S, Yatsuhashi H, Higuchi N, Nakamuta M, Oeda S, Eguchi Y, Shakado S, Sakisaka S, Yoshimaru Y, Sasaki Y, Honma Y, Harada M, Seike M, Maeshiro T, Miuma S, Nakao K, Mawatari S, Ido A, Nagata K, Matsumoto S, Takami Y, Sohda T, Kakuma T, Torimura T
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Journal Title
Hepatol Int.
Volume: 印刷中
Issue: 3
Pages: 293-301
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Effect of direct-acting antivirals on platelet-associated immune G and thrombocytopenia in hepatitis C virus-related chronic liver disease.2019
Author(s)
Honma Y, Shibata M, Hayashi T, Kusanaga M, Ogino N, Minami S, Kumei S, Oe S, Miyagawa K, Senju M, Matsuoka H, Watanabe T, Hiura M, Abe S, Harada M.
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] A young adult patient with nonalcoholic steatohepatitis developed severe gastroesophageal varices associated with severe obesity and diabetes mellitus2018
Author(s)
Honma Y, Sumida K, Ogino N, Kusanaga M, Minami S, Kumei S, Matsuoka H, Watanabe T, Hiura M, Abe S, Shibata M, Harada M
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Journal Title
Case Reports in Gastroenterology
Volume: 12
Issue: 2
Pages: 487-496
DOI
Related Report
Peer Reviewed
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