| Project/Area Number |
18K08166
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 気管支喘息 / アレルギー / ダニ / 気道上皮細胞 / ミトコンドリア新生 / 気道上皮 / 上皮バリア機能 / ミトコンドリア / PGC1alpha / ダニ抗原 / アレルゲン / SRT1720 / 脱アセチル化酵素 / PGC１α / tight junction protein / E-Cadherin |
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| Outline of Final Research Achievements |
This study aimed to clarify whether the peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α), a central regulator of mitochondrial biogenesis, is involved in the disruption of the airway barrier function induced by aeroallergens. BEAS-2B cells were exposed to house dust mite (HDM) and the expressions of PGC-1α and E-cadherin were examined by immunoblotting. The effect of SRT1720, a PGC-1α activator on E-cadhherin experssion and transepithelial electrical resistance (TEER) in the HDM-exposed BEAS-2B cells were investigated. The amounts of PGC-1α and E-cadherin in the HDM-treated cells were significantly decreased compared to the vehicle-treated cells. SRT1720 restored the expressions of PGC-1α and E-cadherin reduced by HDM in BEAS-2B cells. Treatment with SRT1720 also significantly ameliorated the HDM-induced reduction in TEER. In conclusion, the current study demonstrated that HDM disrupted the airway barrier function through the PGC-1α-dependent pathway.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は喘息病態として代表的なアレルゲンであるダニによる気道上皮障害のメカニズムをミトコンドリア新生という今までにない切り口から検討したものである。その中でミトコンドリア新生の主要な調節因子であるPGC-1αがダニ抗原による気道上皮障害に関与していることを示し、PGC-1αの活性作用を持つSRT1720がダニ抗原による気道上皮障害を改善させる作用を持つことが明らかになった。これらの結果から、PGC-1αを標的とした喘息の新規治療戦略が有用である可能性が示唆され、さらに気道上皮機能の回復という今までにない治療薬の開発の基礎になる可能性もあり、本研究は今後の喘息治療の発展に意義のあるものと考える。
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