徳島大学 教育・研究者情報データベース(EDB)

1. 手塚 敏史

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2. 小川 博久([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.病理系.疾患病理学])

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3. 吾妻 雅彦

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4. 後東 久嗣

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5. 上原 久典([徳島大学.病院.診療科.病理診断科])

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6. 青野 純典([徳島大学.大学院ヘルスバイオサイエンス研究部.医療創生科学部門.先端医療創生科学講座.呼吸器・膠原病内科学])

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7. 埴淵 昌毅([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).地域呼吸器・血液・代謝内科学])

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8. (英) Yoichi Yamaguchi

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9. (英) Tomoyuki Fujikawa

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10. (英) Akiko Itai

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11. 西岡 安彦([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.呼吸器・膠原病内科学])

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(英) IMD-4690, a novel specific inhibitor for plasminogen activator inhibitor-1, reduces allergic airway remodeling in a mouse model of chronic asthma via regulating angiogenesis and remodeling-related mediators

(英) Plasminogen activator inhibitor (PAI)-1 is the principal inhibitor of plasminogen activators, and is responsible for the degradation of fibrin and extracellular matrix. IMD-4690 is a newly synthesized inhibitor for PAI-1, whereas the effect on allergic airway inflammation and remodeling is still unclear. We examined the in vivo effects by using a chronic allergen exposure model of bronchial asthma in mice. The model was generated by an immune challenge for 8 weeks with house dust mite antigen, Dermatophagoides pteronyssinus (Dp). IMD-4690 was intraperitoneally administered during the challenge. Lung histopathology, hyperresponsiveness and the concentrations of mediators in lung homogenates were analyzed. The amount of active PAI-1 in the lungs was increased in mice treated with Dp. Administration with IMD-4690 reduced an active/total PAI-1 ratio. IMD-4690 also reduced the number of bronchial eosinophils in accordance with the decreased expressions of Th2 cytokines in the lung homogenates. Airway remodeling was inhibited by reducing subepithelial collagen deposition, smooth muscle hypertrophy, and angiogenesis. The effects of IMD-4690 were partly mediated by the regulation of TGF-, HGF and matrix metalloproteinase. These results suggest that PAI-1 plays crucial roles in airway inflammation and remodeling, and IMD-4690, a specific PAI-1 inhibitor, may have therapeutic potential for patients with refractory asthma due to airway remodeling.

1. (英) Acetates
2. (英) Airway Remodeling
3. (英) Animals
4. (英) Antigens, Dermatophagoides
5. (英) Asthma
6. (英) Biphenyl Compounds
7. (英) Bronchi
8. (英) Bronchoalveolar Lavage Fluid
9. (英) Chronic Disease
10. (英) Cytokines
11. (英) Dermatophagoides pteronyssinus
12. (英) Disease Models, Animal
13. (英) Eosinophils
14. (英) Female
15. (英) Immunoglobulin E
16. (英) Mice
17. (英) Neovascularization, Pathologic
18. (英) Plasminogen Activator Inhibitor 1
19. (英) Tissue Plasminogen Activator

1. (英) Article.ELocationID: 10.1371/journal.pone.0121615

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) OtherID: PMC4364779