Biomarker research for NASH diagnosis based on the disease-related glycoantigen expression in liver-resident macrophages

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K13223
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied health science
• Research Institution: Saga University
• Principal Investigator: Okada Takahiro 佐賀大学, 医学部, 助教 (30584809)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 生活習慣病 / マクロファージ / 糖鎖

Outline of Final Research Achievements

In the present study, the correlation between non-alcoholic steatohepatitis (NASH) progression and glycoantigen expression in liver-resident macrophages (Kupffer cells) was investigated. Using a mouse model, disease-related alteration of protein glycosylation was demonstrated by lectin microarray-based glycoprofiling. In association with the pathogenesis of NASH, the content of membrane protein-bound oligosaccharides harboring galactose/N-acetylgalactosamine residues increased in Kupffer cells. The results also suggested that disease progression altered the degree of oligosaccharide branching. Furthermore, the results of differential gene expression analysis suggested that the up-regulation of B3gnt5 and the down-regulation of St6gal1 were involved in such alteration.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

NASHは早期診断の方法が確立されておらず、自覚症状を伴わないために肝がんや肝硬変への進展リスクが高い生活習慣病である。本研究で得られた結果をもとに、初期病態を反映するような糖鎖抗原の分布について詳細な検討を行っていくことで、クッパー細胞の性状変化に基づく診断バイオマーカーの開発が可能になると考えられる。これを実現化できれば、例えば血液生化学検査のように身体的・精神的負担の少ない病態鑑別が可能となり、子供から老人に至るまで幅広い年代に対して生活習慣病の早期予防を実施できるようになると期待される。