Development of new therapeutic agents for organ fibrosis based on chronic inflammation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08690
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Osaka Metropolitan University (2022-2023); Osaka City University (2021)
• Principal Investigator: Takemura Shigekazu 大阪公立大学, 大学院医学研究科, 特任教授 (00322363)
• Co-Investigator(Kenkyū-buntansha): 椿 一典 京都府立大学, 生命環境科学研究科, 教授 (50303897) ; 南山 幸子 京都府立大学, 生命環境科学研究科, 教授 (00362989)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 臓器線維化 / 肝硬変 / マクロファージ

Outline of Final Research Achievements

In this study, we aimed to develop a new method to suppress organ fibrosis resulting from chronic inflammation through the control of macrophage (MF) polarization. First, eight new compounds were synthesized using S-allyl cysteine as the lead compound. MF derived from rat bone marrow were collected and cultured, and the inhibitory effect on MF polarization induction was examined. X-3 (tentative) and Y-1 (tentative) were confirmed to be more effective than other compounds. The supernatant of MF supplemented with these two substances suppressed collagen production in hepatic stellate cells. In vivo animal experiments are currently being conducted.

Free Research Field

肝臓内科

Academic Significance and Societal Importance of the Research Achievements

従来、肝硬変や肺線維症など慢性炎症に起因する臓器線維化に対する有効な治療法は確立されていない。本研究では、慢性炎症に起因する臓器線維化をマクロファージの分極を制御することにより病態の進行を抑制するという画期的なものである。我々はS-アリルシステイン（ＳＡＣ）がこの効果を有することを以前に報告したが、さらに有効で安定、安全性の高い物質を探索し、2種の新規化合物の有効性をin vitroで確認した。