{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T15:46:06Z","timestamp":1792856766077,"version":"4.5.0"},"reference-count":41,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["NRF-2020M2D9A2093964"],"award-info":[{"award-number":["NRF-2020M2D9A2093964"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["NRF-2023R1A2C20072227"],"award-info":[{"award-number":["NRF-2023R1A2C20072227"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["KIRAMS, 50531-2025"],"award-info":[{"award-number":["KIRAMS, 50531-2025"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Science and ICT (MSIT)","award":["NRF-2020M2D9A2093964"],"award-info":[{"award-number":["NRF-2020M2D9A2093964"]}]},{"name":"Ministry of Science and ICT (MSIT)","award":["NRF-2023R1A2C20072227"],"award-info":[{"award-number":["NRF-2023R1A2C20072227"]}]},{"name":"Ministry of Science and ICT (MSIT)","award":["KIRAMS, 50531-2025"],"award-info":[{"award-number":["KIRAMS, 50531-2025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease with limited therapeutic options and increasing global incidence, with a median survival of only 2\u20135 years. The clinical utility of macrophage polarization to regulate the progression of pulmonary fibrosis remains understudied. This study determined the efficacy of nintedanib and pexidartinib (PLX3397) combination therapy for treating IPF. Combination treatment effectively inhibited the progression of radiation-induced pulmonary fibrosis (RIPF) and prolonged survival in bleomycin-treated mice. Micro-CT analysis revealed a significant tissue repair efficacy. The therapy significantly normalized the abnormal vascular structure observed during RIPF and bleomycin-induced pulmonary fibrosis progression and was accompanied by a decrease in the M2 population. Polarized M1 macrophages enhanced normalized tube formation of irradiated endothelial cells (ECs) in vitro; M2 macrophages increased adhesion in irradiated ECs and abnormal tube formation. Single-cell RNA sequencing data from patients with IPF further supports colony stimulating factor (CSF) 1 upregulation in macrophages and downregulation of capillary EC markers. This study highlights a promising combination strategy to overcome the therapeutic limitations of monotherapy with nintedanib for the treatment of IPF.<\/jats:p>","DOI":"10.3390\/ijms26157570","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T07:45:11Z","timestamp":1754466311000},"page":"7570","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pexidartinib and Nintedanib Combination Therapy Targets Macrophage Polarization to Reverse Pulmonary Fibrosis: A Preclinical Study"],"prefix":"10.3390","volume":"26","author":[{"given":"Ji-Hee","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Kyung","family":"Nam","sequence":"additional","affiliation":[{"name":"Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Sik","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungyoul","family":"Seo","sequence":"additional","affiliation":[{"name":"Agathonbio Co., Ltd., Hwaseong-si 18487, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung Chul","family":"Ryu","sequence":"additional","affiliation":[{"name":"Independent Researcher, Hwaseong-si 18487, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae-June","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea"},{"name":"College of Veterinary Medicine, Jeju National University, Jeju 63243, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeeyong","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3110-0384","authenticated-orcid":false,"given":"Yoon-Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1186\/s12931-019-1161-4","article-title":"Antifibrotic therapy for idiopathic pulmonary fibrosis: Time to treat","volume":"20","author":"Maher","year":"2019","journal-title":"Respir Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Krauss, E., Tello, S., Wilhelm, J., Schmidt, J., Stoehr, M., Seeger, W., Dartsch, R.C., Crestani, B., and Guenther, A. 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