{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T18:46:24Z","timestamp":1787856384558,"version":"build-2784847793"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>FGFs (fibroblast growth factors) are major factors associated with the pathogenesis of pulmonary fibrosis. On the one hand, 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. On the other hand, recent reports suggest that FGFs are required for epithelial recovery. In this study, we focused on FGF signaling to both fibroblasts and alveolar epithelial cells (AECs), and we examined the effect of a pan-FGFR blocker on experimental pulmonary fibrosis in mice. 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 IB or flow cytometry. We also investigated the effect of BGJ398 on pulmonary fibrosis induced by bleomycin in mice. 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 resulting from alveolar injury and inhibition of AEC regeneration. These data suggest that the total inhibition of FGFR signaling can suppress lung fibrosis by inhibiting fibroblast activities, although alveolar injury is simultaneously caused.<\/jats:p>","DOI":"10.1165\/rcmb.2019-0090oc","type":"journal-article","created":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T15:05:29Z","timestamp":1587999929000},"page":"317-326","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":14,"title":["Blockade of Pan-Fibroblast Growth Factor Receptors Mediates Bidirectional Effects in Lung Fibrosis"],"prefix":"10.1093","volume":"63","author":[{"given":"Shun","family":"Morizumi","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine and Rheumatology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seidai","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Rheumatology, 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