Elucidation of the mechanisms of pulmonary fibrosis and identification of therapeutic target molecules.

2024 Fiscal Year Final Research Report

• Project/Area Number: 22K08282
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Kyoto University
• Principal Investigator: Toyomoto Masayasu 京都大学, 医学研究科, 特定准教授 (20600505)
• Project Period (FY): 2022-04-01 – 2025-03-31
• Keywords: 肺線維症 / 上皮障害 / フェロトーシス / 創薬 / 新規化合物 / 実用化

Outline of Final Research Achievements

In this study, we screened lipid peroxidation inhibitors using a custom-developed assay system designed to identify novel ferroptosis inhibitors. Using this system, we demonstrated that lipid peroxidation contributes to neutrophil extracellular trap (NET) formation, also known as NETosis, occurring in the early phase of lung inflammation (PMID: 39631397). These findings suggest that inhibition of lipid peroxidation may offer a therapeutic strategy for diseases characterized by excessive neutrophil activation. Furthermore, in collaborative research, a novel ferroptosis inhibitor was shown to have protective effects on lung function in a rat model of lung transplantation-associated ischemia-reperfusion injury (PMID: 40307436). Based on these findings, we have filed a patent application focusing on the practical application of this novel ferroptosis inhibitor.

Free Research Field

創薬科学

Academic Significance and Societal Importance of the Research Achievements

学術的意義：肺の炎症や虚血再灌流障害は、肺組織の障害から肺線維化を誘発させる。本研究で肺障害が脂質過酸化抑制剤や新規フェロトーシス阻害剤によって改善できることを見出し、論文公開によって学術的意義が示された。
社会的意義：線維化機序に基づいた創薬研究は、肺線維症、特に指定難病である特発性肺線維症の治療法進展につながると期待できる。本研究では肺組織障害に対する創薬研究から、脂質過酸化抑制剤・新規フェロトーシス阻害剤の有効性が示され、新規化合物の実用化研究を推進させるための特許出願によって社会的意義の証明が前進した。