Functional analysis of fibrosis-promoting molecules specifically expressed in myofibroblasts and laying the foundations for their drug discovery applications.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03383
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Kyushu University
• Principal Investigator: Michio Nakaya 九州大学, 薬学研究院, 准教授 (80464387)
• Co-Investigator(Kenkyū-buntansha): 小迫 英尊 徳島大学, 先端酵素学研究所, 教授 (10291171)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 筋線維芽細胞 / 線維化

Outline of Final Research Achievements

Non-alcoholic steatohepatitis (NASH), which has been on the rise in recent years, is a condition of increased fibrosis resulting from inflammation caused by excessive fat accumulation. Fibrosis leads to loss of function due to hardening and eventually to serious conditions such as cirrhosis and liver cancer. However, there is currently no definitive treatment for NASH. We therefore looked for targets that could lead to the development of fibrosis-targeted NASH therapies.
We found a protein that promote fibrosis is only expressed during fibrosis and is specifically expressed in myofibroblasts, the cells responsible for fibrosis.In addition, fibrosis of the liver during NASH was significantly reduced in knockout mice of this protein.

Free Research Field

分子生物学、薬理学、生化学

Academic Significance and Societal Importance of the Research Achievements

今回、新たに肝臓の線維化を促進するタンパク質を同定することができた。同定したタンパク質は、マウスおよびヒト共に線維化した肝臓において、活性化した肝星細胞に特異的に発現する。また、正常時の肝臓にはほとんど発現しない。従って、このタンパク質は、非アルコール性脂肪肝炎時やウイルス感染時などの肝臓の線維化治療の標的分子になる可能性が考えられる。今後はこのタンパク質がコラーゲンなどの産生を促進するメカニズムを詳細に解析する予定である。