Investigating the role of mucin in pulmonary fibrosis-associated microbiota dysbiosis using MUC5B overexpressing mice

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08564
• 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: Mie University
• Principal Investigator: Gabazza Esteban 三重大学, 医学系研究科, 教授 (00293770)
• Co-Investigator(Kenkyū-buntansha): 戸田 雅昭 三重大学, 医学系研究科, 講師 (10202201) ; 竹下 敦郎 三重大学, 医学系研究科, 助教 (10830490) ; 安間 太郎 三重大学, 医学系研究科, 助教 (80773887) ; 小林 哲 三重大学, 医学部附属病院, 准教授 (20437114)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 細菌叢 / 細胞死 / corisin / 肺線維症 / ムチン / MUC5B / 抗線維化剤 / 予後

Outline of Final Research Achievements

Genome-wide linkage study has shown that patients with a single nucleotide polymorphism (rs35705950) of MUC5B have a 20-fold increased risk of developing idiopathic pulmonary fibrosis. Recently, it has been reported that microbiota dysbiosis in the lungs is involved in the progression of idiopathic pulmonary fibrosis. Therefore, in this study, we used MUC5B overexpression transgenic (TG) mice and wild-type mice to examine the characteristics of microbiota in the lungs and its involvement in the pathogenesis of pulmonary fibrosis. As a result, we found that the expression of corisin, a microbiota-derived cell death inducer, was high in MUC5B-TG mice and wild-type mice with pulmonary fibrosis and that it was involved in the promotion of inflammation and the pathogenesis of pulmonary fibrosis. Furthermore, we also found that anti-corisin monoclonal antibody had an inhibitory effect on pulmonary fibrosis.

Free Research Field

呼吸器内科・免疫

Academic Significance and Societal Importance of the Research Achievements

本研究では、肺線維症マウスモデルを用いて、細菌由来細胞死誘導ペプチドが肺線維症の病態形成に関与することと抗corisinモノクローナル中和抗体が治療薬として有効であることを明らかにした。本研究で得た結果は抗肺線維化剤の開発につながる可能性があり、社会的意義が高いと考えられる。