Explore novel treatment target for lung fibrosis using alveolar organoid

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17238
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Enomoto Yasunori 国立研究開発法人理化学研究所, 生命機能科学研究センター, 基礎科学特別研究員 (90865297)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 肺線維症 / 肺胞オルガノイド / 組織幹細胞

Outline of Final Research Achievements

Although the pathogenesis of lung fibrosis has been believed to start with epithelial injury or cellular senescence, the molecular mechanism remains elusive.
In this study, we used alveolar organoid technology and established in vitro lung fibrosis model by coculturing primary lung fibroblasts, in which we can evaluate the process of differentiation of the fibroblasts into myofibroblasts. Using this model, we revealed that damaged alveolar epithelial cell type 2 (AT2) could produce active TGFβ and directly induce myofibroblast differentiation. Additionally, we found that the pro-fibrotic potential of AT2 could be enhanced by their autocrine TGFβ signal. These findings were validated even in human AT2.

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

肺線維症は予後不良な難治性肺疾患である。従来の肺線維症治療薬は、線維芽細胞を主たる治療標的としており、また効果の面では残念ながら進行の抑制までしか成しえていない。
本研究では、本症の発症起点と考えられている肺胞上皮傷害に着目し、in vitroの肺線維症モデルを確立することで、病態のさらなる解明に迫った。研究結果は、既存薬ではアプローチできていない新規治療標的を示唆するものであり、今後の新薬開発への発展が期待される。