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ID 115073
タイトル別表記
汎FGF受容体阻害は肺線維症に対して二面性の作用を示す
Dual effects of FGFR inhibition in lung fibrosis
著者
森住, 俊 徳島大学大学院医科学教育部(医学専攻) 徳島大学 教育研究者総覧
Okazaki, Hiroyasu Tokushima University
Chen, Yajuan Tokushima University
Nishimura, Haruka Tokushima University
キーワード
Fibroblast growth factor
Pulmonary fibrosis
Epithelial recovery
資料タイプ
学位論文
抄録
[Rationale] Fibroblast growth factors (FGF) are major factors associated with the pathogenesis of pulmonary fibrosis. Nintedanib, a tyrosine kinase inhibitor targeting several growth factor receptors including the FGF receptor (FGFR), has been approved for the treatment of idiopathic pulmonary fibrosis (IPF). On the other hand, recent reports suggest that FGF are required for epithelial recovery. In this study, we focused on FGF signaling to both fibroblasts and alveolar epithelial cells (AECs), and examined the effect of a pan-FGFR blocker on experimental pulmonary fibrosis in mice.
[Methods] The effects of BGJ398, a pan-FGFR inhibitor, on the migration and proliferation of fibroblasts and AECs were assessed using transwell migration or 3H-thymidine incorporation assays. The expression of FGFR was analyzed using immunoblot or flow cytometry. We also investigated the effect of BGJ398 on the pulmonary fibrosis induced by bleomycin in mice.
[Results] Both lung fibroblasts and AECs expressed FGFRs. BGJ398 significantly inhibited the proliferation and migration of lung fibroblasts stimulated with FGF2. BGJ398 also reduced the proliferation of AECs in response to FGF2. Although the administration of BGJ398 ameliorated pulmonary fibrosis in bleomycin-treated mice, it increased mortality due to alveolar injury and inhibition of AEC regeneration.
[Conclusions] These data suggest that the total inhibition of FGFR signaling can suppress lung fibrosis by inhibiting fibroblast activities, although alveolar injury is simultaneously caused.
掲載誌名
American Journal of Respiratory Cell and Molecular Biology
ISSN
15354989
cat書誌ID
AA12060923
出版者
American Thoracic Society
63
3
開始ページ
317
終了ページ
326
発行日
2020-04-27
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Shun Morizumiの学位論文として提出され,学位審査・授与の対象となっている。
Originally Published in: Shun Morizumi, Seidai Sato, Kazuya Koyama, Hiroyasu Okazaki, Yajuan Chen, Hisatsugu Goto, Kozo Kagawa, Hirohisa Ogawa, Haruka Nishimura, Hiroshi Kawano, Yuko Toyoda, Hisanori Uehara, Yasuhiko Nishioka. Blockade of Pan-Fibroblast Growth Factor Receptors Mediates Bidirectional Effects in Lung Fibrosis. American Journal of Respiratory Cell and Molecular Biology 2020; Volume 63, Issue 3: Pages 317-326.
The final publication is available at https://www.atsjournals.org/doi/10.1165/rcmb.2019-0090OC
権利情報
Copyright © 2020 by the American Thoracic Society
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3430号
学位記番号
甲医第1460号
学位授与年月日
2020-07-30
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系
病院