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To this end, the model was rigorously evaluated for reproducible phenotype and TGF\u03b2\u2010directed treatment outcomes. Lung disease was profiled longitudinally in male C57BL6\/JRJ mice receiving a single intratracheal instillation of BLEO (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200910\u201312 per group). A TGF\u03b2R1\/ALK5 inhibitor (ALK5i) was profiled in six independent studies in BLEO\u2010IPF mice, randomized\/stratified to treatment according to baseline body weight and non\u2010invasive whole\u2010body plethysmography. ALK5i (60\u2009mg\/kg\/day) or vehicle (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200910\u201316 per study) was administered orally for 21\u2009days, starting 7\u2009days after intratracheal BLEO installation. BLEO\u2010IPF mice recapitulated functional, histological and biochemical hallmarks of IPF, including declining expiratory\/inspiratory capacity and inflammatory and fibrotic lung injury accompanied by markedly elevated TGF\u03b2 levels in bronchoalveolar lavage fluid and lung tissue. Pulmonary transcriptome signatures of inflammation and fibrosis in BLEO\u2010IPF mice were comparable to reported data in IPF patients. ALK5i promoted reproducible and robust therapeutic outcomes on lung functional, biochemical and histological endpoints in BLEO\u2010IPF mice. The robust lung fibrotic disease phenotype, along with the consistent and reproducible lung protective effects of ALK5i treatment, makes the spirometry\u2010confirmed BLEO\u2010IPF mouse model highly applicable for profiling novel drug candidates for IPF.\n                  <\/jats:p>","DOI":"10.14814\/phy2.70077","type":"journal-article","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T22:35:32Z","timestamp":1728686132000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Reproducible lung protective effects of a TGF\u03b2R1\/ALK5 inhibitor in a bleomycin\u2010induced and spirometry\u2010confirmed model of IPF in male mice"],"prefix":"10.14814","volume":"12","author":[{"given":"Asbj\u00f8rn Graver","family":"Petersen","sequence":"first","affiliation":[{"name":"Gubra  H\u00f8rsholm Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie H.","family":"Korntner","sequence":"additional","affiliation":[{"name":"Gubra  H\u00f8rsholm Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamal","family":"Bousamaki","sequence":"additional","affiliation":[{"name":"Gubra  H\u00f8rsholm Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Or\u00f3","sequence":"additional","affiliation":[{"name":"Gubra  H\u00f8rsholm Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba Manresa","family":"Arraut","sequence":"additional","affiliation":[{"name":"Gubra  H\u00f8rsholm Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne E.","family":"Pors","sequence":"additional","affiliation":[{"name":"Gubra  H\u00f8rsholm Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casper Gravesen","family":"Salinas","sequence":"additional","affiliation":[{"name":"Gubra  H\u00f8rsholm Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja Worm","family":"Andersen","sequence":"additional","affiliation":[{"name":"Gubra  H\u00f8rsholm Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin R\u00f8nn","family":"Madsen","sequence":"additional","affiliation":[{"name":"Gubra  H\u00f8rsholm Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaohui","family":"Nie","sequence":"additional","affiliation":[{"name":"Enanta Pharmaceuticals  Watertown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Butts","sequence":"additional","affiliation":[{"name":"Enanta Pharmaceuticals  Watertown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Roqueta\u2010Rivera","sequence":"additional","affiliation":[{"name":"Enanta Pharmaceuticals  Watertown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Simonsen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Pulmonary and Cardiovascular Pharmacology, Faculty of Health Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3732-0281","authenticated-orcid":false,"given":"Henrik H.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Gubra  H\u00f8rsholm Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Feigh","sequence":"additional","affiliation":[{"name":"Gubra  H\u00f8rsholm Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3810"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/36.9.3403967"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0276-y"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.41.4.467"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39717"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201204-0754OC"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2015.11.013"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2018.07.002"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2019.02.005"},{"key":"e_1_2_10_11_1","unstructured":"Chollet F. et\u00a0al. 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