Development of serum biomarkers and therapeutic strategy for non-alcoholic steatohepatitis using liver-specific apoptosis-prone mice
| Project/Area Number |
17K08994
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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 |
Laboratory medicine
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| Research Institution | Toho University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山崎 創 東邦大学, 医学部, 准教授 (70315084)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 非アルコール性脂肪性肝炎 / アポトーシス / 増殖因子 / 肝再生 / 血清バイオマーカー / cFLIP / 肝前駆細胞 |
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| Outline of Final Research Achievements |
Non-alcoholic steatohepatitis (NASH) progresses to liver cirrhosis and hepatocellular carcinoma, but specific treatment has not been established. Highly invasive liver biopsy is currently required for NASH diagnosis, and less invasive blood test using specific serum biomarkers is awaited. By using pathological NASH model in gene-manipulated mice, we identified that one growth factor, FGF18, was upregulated upon hepatocyte death and induced the proliferation of hepatocytes in NASH liver. Moreover, we also found that serum FGF18 was increased in human NASH patients, suggesting that FGF18 can be used as a new serum biomarker for NASH diagnosis.
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| Academic Significance and Societal Importance of the Research Achievements |
非アルコール性脂肪性肝疾患(NAFLD)は、飲酒量が少ないにも関わらず肝臓に脂肪が蓄積する疾患である。患者の一部はNASHに進行するが、発症メカニズムは不明な点が多く、有効な治療法も確立していない。またNASHの確定診断に用いられる肝生検は侵襲性が高いことから、血液を用いた侵襲性の低い診断方法の開発が求められている。本研究成果は血液を用いた新たなNASH診断法の開発に貢献するとともに、発症メカニズムの理解と治療法の開発につながる。
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Report
(4 results)
Research Products
(25 results)
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[Journal Article] Necroptosis of intestinal epithelial cells induces type 3 innate lymphoid cell-dependent lethal ileitis.2019
Author(s)
Shindo R, Ohmuraya M, Komazawa-Sakon S, Miyake S, Deguchi Y, Yamazaki S, Nishina T, Yoshimoto T, Kakuta S, Koike M, Uchiyama Y, Konishi H, Kiyama H, Mikami T, Moriwaki K, Araki K, Nakano H.
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Journal Title
iScience
Volume: 15
Pages: 536-551
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] 肝特異的cFLIP低発現マウスを用いた肝障害モデルの解析2017
Author(s)
山﨑 創, 朴 雪花, 駒澤-左近 幸子, 三宅 早苗, 中林 修, 田中 稔, 大村谷 昌樹, 及川 彰, 角田 宗一郎, 内山 安男, 田中 正人, 中野 裕康
Organizer
第26回日本Cell Death学会学術集会
Related Report
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[Presentation] RORgt陽性細胞はRIPK3およびMLKL依存性に小腸炎を誘導する2017
Author(s)
進藤 綾大, 大村谷 昌樹, 駒澤 幸子, 三宅 早苗, 山﨑 創, 仁科 隆史, 小西 博之, 木山 博資, 三上 哲夫, 荒木 喜美, 中野 裕康
Organizer
第26回日本Cell Death学会学術集会
Related Report
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