Development of serum biomarkers and therapeutic strategy for non-alcoholic steatohepatitis using liver-specific apoptosis-prone mice

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08994
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Toho University
• Principal Investigator: TSUCHIYA Yuichi 東邦大学, 医学部, 講師 (10307738)
• Co-Investigator(Kenkyū-buntansha): 山崎 創 東邦大学, 医学部, 准教授 (70315084)
• Project Period (FY): 2017-04-01 – 2020-03-31
• 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

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.

Free Research Field

生化学

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。