Search for new cell- or small molecule-based therapies to promote regression of liver cirrohsis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05282
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• 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): 大西 俊介 北海道大学, 医学研究院, 准教授 (10443475) ; 須田 剛生 北海道大学, 大学病院, 特任助教 (20447460) ; 森川 賢一 北海道大学, 医学研究院, 助教 (60384377)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 肝線維化

Outline of Final Research Achievements

The present study was conducted to search for therapeutic candidates (peptides, small molecules and miRNAs) to target liver fibrosis and activation of hepatic stellate cells and to analyze their mechanisms of action. The main results are as follows; (1) We confirmed suppressive effects of liver fibrosis and inflammation of exosomes derived from the culture supernatant of human amniotic membrane-derived mesenchymal stem cells. (2) palmitoylethanolamide (PEA) inhibited activation of hepatic stellate cells through PPAR-independent mechanisms. (3) Comprehensive glycan modification structure analysis indentified fucosyl modification of serum proteins as markers that associate with NAFL to NASH progression. (4) Comprehensive analysis of microRNAs related to cultured hepatic stellate cell activation identified miRNAs that up- or down-regulated in activated stellate cells.

Free Research Field

消化器内科学

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。