Elucidation of the pathogenesis of pulmonary fibrosis and development of novel treatment based on cold-inducible RNA-binding protein

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08176
• 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: Hamamatsu University School of Medicine
• Principal Investigator: Hozumi Hironao 浜松医科大学, 医学部, 助教 (40771457)
• Co-Investigator(Kenkyū-buntansha): 須田 隆文 浜松医科大学, 医学部, 教授 (30291397)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 肺線維症 / 低温誘導性RNA結合タンパク / ブレオマイシン / CIRBP / 線維芽細胞

Outline of Final Research Achievements

Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis and the development of novel therapies is an unmet medical need. We previously reported that cold-inducible RNA-binding protein (CIRBP) is highly expressed in the lungs of IPF patients, which is associated with poor prognosis. In this study, we investigated the role of CIRBP in pulmonary fibrosis using the bleomycin (BLM) model. Compared to wild-type mice, BLM-induced pulmonary fibrosis was ameliorated in CIRBP knockout mice. Administration of CIRBP inhibitors to wild-type mice attenuated BLM-induced pulmonary fibrosis, indicating that inhibition of CIRBP may be a promising therapeutic candidate for pulmonary fibrosis. We plan to further analyze the mechanism of CIRBP in fibroblasts.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

特発性肺線維症（IPF）は，日常診療での遭遇頻度が高く，平均生存期間3～4年で呼吸不全死に至りうる，きわめて予後不良な疾患である．抗線維化薬であるピルフェニドンとニンテダニブが承認されており，それぞれ呼吸機能の悪化を遅らせる効果が証明されているが，生存期間を大幅に改善する治療法は確立していない．本研究の結果，CIRBPの阻害が肺線維症の有望な治療薬候補となりうることが明らかになった．本研究は，IPFを中心とした肺線維症の病態解明や治療薬開発に大きな貢献が期待できるだけでなく，その他の線維化性疾患に対する治療への応用も期待できる研究である．