Increased LHX9 expression in alveolar epithelial type 2 cells of patients with chronic obstructive pulmonary disease

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08134
• 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: Tohoku University
• Principal Investigator: Yamada Mitsuhiro 東北大学, 大学病院, 講師 (00396483)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: COPD

Outline of Final Research Achievements

Although we previously reported that LHX9 mRNA expression was up-regulated in AT2 cells of COPD lung tissues, it is yet to be elucidated how LHX9 is associated with the vulnerability of AT2 cells in COPD. In this study, we revealed that LHX9 mRNA expression was increased in AT2 cells from COPD lung tissues, compared to non-COPD. The airflow obstruction was independently correlated with the increase in LHX9 expression. Among several pro-inflammatory cytokines, interferon-γ was a strong inducer for LHX9 expression in A549 cells. Lhx9 was involved in the increased susceptibility to serum starvation-induced cell death of A549 cells. Our data suggest that IFN-γ predominantly increases the LHX9 expression which enhances the susceptibility to cell death. Considering the independent association of the increased LHX9 expression in AT2 cells with airflow obstruction, the IFN-γ-Lhx9 axis might contribute to the vulnerability of AT2 cells in the lungs of COPD.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究はLHX9によるⅡ型細胞の機能制御がCOPD病態の形成に重要な役割を持っている可能性を示唆した。現在行われているCOPDに対する治療は、気管支拡張薬やテオフィリン製剤を用いた気流閉塞の解除が主体であり、気道・肺組織のリモデリング制御等、根本的な治療は開発されていない。本研究結果から、COPDのⅡ型細胞の脆弱性にはIFNγ-LHX9シグナル伝達経路が関与している可能性が示唆されたが、COPDにおいてこの経路を抑制することで、COPD肺組織においてⅡ型細胞の幹細胞活性を維持できる可能性がある。このことは、現在世界中の脅威となっているCOVID-19肺炎の重症化阻止にも役立つ可能性がある。