Relationship between clock genes and in vivo bacterial flora in obesity-associated asthma

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17185
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Kagoshima University
• Principal Investigator: TAKAGI KOICHI 鹿児島大学, 医歯学総合研究科, 特任助教 (40707866)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 気管支喘息 / 肥満 / 時計遺伝子 / CD36 / オゾン / エクソソーム

Outline of Final Research Achievements

Expressions of PGC-1a and CD36, which have been reported to be involved in both obesity and asthma, were suppressed by adding trichostatin A (TSA), an HDAC inhibitor, to cultured cells of lung fibroblasts. It has been reported that the activation of HDAC is regulated through the clock gene in the pathological condition of obesity, and it is suspected that HDAC is involved in the pathological condition of obesity-associated asthma. In addition, in an asthma model created by combining OVA sensitization and exposure with ozone exposure, obese mice prepared by ingesting a high-fat diet showed a significant increase in airway hyperresponsiveness and Th2 cytokines compared to control.

Free Research Field

喘息・COPD

Academic Significance and Societal Importance of the Research Achievements

気道構成細胞において、喘息と肥満の双方の病態に関わるPGC-1α、CD36がHDACの活性化により制御を受けることが確認されたことで、HDAC及びHDACの活性化を制御する時計遺伝子が肥満合併喘息の難治化に関わる可能性が示された。培養細胞で認められた上記の反応が肥満マウスの喘息モデルの気道内で同様の反応が認められるか確認することで、HDAC及びHDACの活性化を制御する時計遺伝子が新たな肥満合併喘息の治療薬開発につながる可能性がある。また、今回の研究では喘息の病態を患者から採取したエクソソームで解析する新たな試みを行っており、今後の新しい研究手技についても検討を行っている。