2021 Fiscal Year Final Research Report

Comprehensive screening of miviroenvirinmental factors that affect liver fibrosis

Research Project

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Project/Area Number	19H03630
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 53010:Gastroenterology-related
Research Institution	Hokkaido University
Principal Investigator	Sakamoto Naoya 北海道大学, 医学研究院, 教授 (10334418)
Co-Investigator(Kenkyū-buntansha)	須田剛生北海道大学, 大学病院, 特任助教 (20447460) 古川潤一北海道大学, 医学研究院, 特任准教授 (30374193) 森川賢一北海道大学, 医学研究院, 准教授 (60384377) 大西俊介北海道大学, 医学研究院, 准教授 (10443475)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	肝線維化 / 糖鎖修飾
Outline of Final Research Achievements	1. Comprehensive analysis of serum glycan modification structures revealed that the expression of A2F bisect glycans is upregulated in patients with advanced liver fibrosis in NASH. 2. We identified several carrier proteins of A2F bisect glycans including IgA. We identified several carrier proteins of A2F bisect glycans, including IgA. 3. Comprehensive analysis of micro RNAs associated with the activation of cultured hepatic astrocytes revealed that miR-29a, miR-449a, and other specific miRNAs were highly expressed in activated astrocytes and regulated the expression of proteins in the cytoskeleton, extracellular matrix, and chemotaxis-related pathways by pathway analysis. 4. serum Ang2 was significantly elevated in hepatitis C post-SVR carcinoma cases.
Free Research Field	肝臓病学
Academic Significance and Societal Importance of the Research Achievements	本研究の成果は、肝星細胞を標的とした細胞・薬物療法による肝線維化の組織修復を促進する治療法開発の基盤となる。肝疾患と糖鎖発現変動に関する研究は多数報告があるが、主要な全てのクラスの糖鎖の包括的な解析例はない。包括的糖鎖修飾解析の結果同定された特異修飾糖鎖は、非侵襲的診断マーカーとしてのみならず、糖鎖構造に対する抗体、結合小分子を大規模探索し、糖鎖修飾構造を標的とした分子標的治療が構築される可能性がある。