2018 Fiscal Year Final Research Report
New anti-inflammatory strategy for the pathogenesis of chronic obstructive pulmonary disease
| Project/Area Number |
16H05307
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Research Collaborator |
Sugiura Hisatosi
Yamada Mitsuhiro
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 細胞老化 / 酸化型コレステロール / エピゲノム変化 |
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| Outline of Final Research Achievements |
In the current project, we found that the amounts of plasma growth differentiation factor 11 (GDF11) in the COPD patients were decreased compared to those of the healthy subjects as well as in the lungs. The amounts of plasma GDF11 were significantly correlated with the data of lung function. GDF11 was mainly expressed in the bronchial epithelial cells and lung fibroblasts. The expression of GDF11 in the lungs of COPD was significantly less than in those of healthy subjects. Administration of GDF11 was attenuated the elastase-induced cellular senescence and enlargement of airspace. Oxysterol was highly expressed in the lungs of COPD compared to healthy subjects. Oxysterol accelerated cellular senescence of the lung fibroblasts through nitrosative stress. Further, we found that the expression of CD169 in the COPD alveolar macrophages, which was involved in phagocytosis of bacteria was significantly attenuated compared to that in the control subjects.
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| Free Research Field |
呼吸器内科
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| Academic Significance and Societal Importance of the Research Achievements |
COPDにおける抗炎症治療の確立にはCOPDの病態をさらに解明する必要がある。我々は全身及び肺における抗老化因子GDF11の発現がCOPD患者において低下していることを明らかにした。さらにCOPD患者の肺および気道では酸化型コレステロールの発現が増強しており細胞老化に関与すること、COPDの肺胞マクロファージでは細菌貪食受容体の発現が低下していることを明らかにした。これらの知見は呼吸器領域のトップジャーナルに掲載されており、新規創薬の基礎研究となりうる重要な知見と考える。
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