Blockade of Pan-Fibroblast Growth Factor Receptors Mediates Bidirectional Effects in Lung Fibrosis

• Material Type: 博士論文
• ISSN: 1535-4989
• Title: Blockade of Pan-Fibroblast Growth Factor Receptors Mediates Bidirectional Effects in Lung Fibrosis
• Volume: 63 3
• Author/Editor: Morizumi, Shun; Sato, Seidai; Koyama, Kazuya; Okazaki, Hiroyasu; Chen, Yajuan; Goto, Hisatsugu; Kagawa, Kozo; Ogawa, Hirohisa; Nishimura, Haruka; Kawano, Hiroshi; Toyoda, Yuko; Uehara, Hisanori; Nishioka, Yasuhiko
• Author Heading: Morizumi, Shun; Sato, Seidai; Koyama, Kazuya; Okazaki, Hiroyasu; Chen, Yajuan; Goto, Hisatsugu; Kagawa, Kozo; Ogawa, Hirohisa; Nishimura, Haruka; Kawano, Hiroshi; Toyoda, Yuko; Uehara, Hisanori; Nishioka, Yasuhiko
• Publication, Distribution, etc.: American Thoracic Society
• Publication Date: 2020-04-27
• Publication Date (W3CDTF): 2020-04-27
• Alternative Title: 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
• Periodical title: American Journal of Respiratory Cell and Molecular Biology
• Degree grantor/type: 徳島大学
• Date Granted: 2020-07-30
• Date Granted (W3CDTF): 2020-07-30
• Dissertation Number: 甲第3430号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第3430号
• Text Language Code: eng
• Subject Heading: Fibroblast growth factor; Pulmonary fibrosis; Epithelial recovery
• Target Audience: 一般
• Note (General): [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.
• DOI: info:doi/10.1165/rcmb.2019-0090OC; https://doi.org/info:doi/10.1165/rcmb.2019-0090OC
• Persistent ID (NDL): info:ndljp/pid/11671530; https://dl.ndl.go.jp/pid/11671530
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2021-05-16T23:51:55+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/115073
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp