活性化トロンビンによる気道リモデリング誘導機序に関する検討(第4回日本アレルギー学会学術大会賞受賞論文)  [in Japanese] POTENTIAL MECHANISMS OF AIRWAY REMODELING INITIATED BY ACTIVATED THROMBIN IN ASTHMA  [in Japanese]

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Author(s)

    • 金澤 博 Kanazawa Hiroshi
    • 大阪市立大学大学院医学研究科呼吸器病態制御内科学 Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University
    • 姜 成勲 Kyoh Shigenori
    • 大阪市立大学大学院医学研究科呼吸器病態制御内科学 Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University
    • 栩野 吉弘 [他] Tochino Yoshihiro
    • 大阪市立大学大学院医学研究科呼吸器病態制御内科学 Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University
    • 児玉 豊城 Kodama Toyoki
    • 大阪市立大学大学院医学研究科呼吸器病態制御内科学 Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University
    • 浅井 一久 Asai Kazuhisa
    • 大阪市立大学大学院医学研究科呼吸器病態制御内科学 Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University
    • 平田 一人 Hirata Kazuto
    • 大阪市立大学大学院医学研究科呼吸器病態制御内科学 Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University

Abstract

【背景・目的】近年,トロンビンは気道リモデリング誘導因子の一つとして注目されている.今回,活性化トロンビンによる気道リモデリング誘導機序を明らかにすることを試みた.【方法】21例の喘息患者,11例の健常者を対象に誘発喀痰を採取し,喀痰上清中のトロンビン活性,basic fibroblast growth factor(bFGF),vascular endothelial growth factor(VEGF),procollagen type III peptide(P-III-P)濃度を測定した.【結果】喘息群の誘発喀痰中トロンビン活性は,健常群に比較し,有意に高値であった.そして,気道内トロンビン活性とVEGF濃度は有意な相関関係を示した.同様に,トロンビン活性とbFGF濃度との間においても有意な相関関係を認めた.さらに,喘息患者においては,bFGFとP-III-P濃度の間に有意な相関関係を認めた.【結語】喘息気道において,トロンビンによりbFGFが活性化される可能性が示唆された.今後,喘息気道におけるトロンビン活性の制御が,気道リモデリング進展抑制に対する一つの治療標的となりうる可能性が示唆された.

Background: High expression of vascular endothelial growth factor (VEGF) induces subepithelial fibrosis associated with angiogenesis in asthma. Thrombin is recognized as a new candidate mediating airway remodeling. Therefore, this study was designed to determine the potential mechanisms of airway remodeling initiated by activated thrombin in asthma. Methods: Levels of biochemical parameters in induced sputum were examined in 21 asthmatic patients and 11 normal controls. Results: Thrombin activity in induced sputum was significantly higher in asthmatic patients than in normal controls (normal controls: median [range] 1.26 (0.93-2.42)U/mL; asthmatic patients: 3.67 (1.15-10.2)U/mL, p<0.0001). VEGF level in induced sputum was positively correlated with thrombin activity in all study subjects. Levels of basic fibroblast growth factor (bFGF), which is a major profibrotic factor, were also significantly higher in asthmatic patients than in normal controls. Moreover, thrombin activity was significantly correlated with bFGF level in all study subjects. We also observed a significant correlation between bFGF and procollagen type III peptide level. Conclusion: Increase in VEGF level leads to up-regulation of thrombin activity in asthmatic airways, and this elevated thrombin activity induces elevation of bFGF level. It will become to be a new strategy of asthma therapy to attenuate thrombin activity for the regulation of airway remodeling.

Journal

  • Japanese Journal of Allergology

    Japanese Journal of Allergology 58(5), 554-559, 2009

    Japanese Society of Allergology

References:  15

Codes

  • NII Article ID (NAID)
    110007337983
  • NII NACSIS-CAT ID (NCID)
    AN00012583
  • Text Lang
    JPN
  • Article Type
    ART
  • ISSN
    0021-4884
  • NDL Article ID
    10335423
  • NDL Source Classification
    ZS9(科学技術--医学--病理学・微生物学・寄生虫学・感染・免疫学・血清学・アレルギー)
  • NDL Call No.
    Z19-32
  • Data Source
    CJP  NDL  NII-ELS  J-STAGE 
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