{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T19:59:58Z","timestamp":1780343998274,"version":"3.54.1"},"reference-count":43,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T00:00:00Z","timestamp":1711584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2020M2D9A2093976"],"award-info":[{"award-number":["NRF-2020M2D9A2093976"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2021R1I1A1A01044625"],"award-info":[{"award-number":["NRF-2021R1I1A1A01044625"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2022R1A2C3011611"],"award-info":[{"award-number":["NRF-2022R1A2C3011611"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1A5A2025286"],"award-info":[{"award-number":["2018R1A5A2025286"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In a recent stereotactic body radiation therapy animal model, radiation pneumonitis and radiation pulmonary fibrosis were observed at around 2 and 6 weeks, respectively. However, the molecular signature of this model remains unclear. This study aimed to examine the molecular characteristics at these two stages using RNA-seq analysis. Transcriptomic profiling revealed distinct transcriptional patterns for each stage. Inflammatory response and immune cell activation were involved in both stages. Cell cycle processes and response to type II interferons were observed during the inflammation stage. Extracellular matrix organization and immunoglobulin production were noted during the fibrosis stage. To investigate the impact of a 10 Gy difference on fibrosis progression, doses of 45, 55, and 65 Gy were tested. A dose of 65 Gy was selected and compared with 75 Gy. The 65 Gy dose induced inflammation and fibrosis as well as the 75 Gy dose, but with reduced lung damage, fewer inflammatory cells, and decreased collagen deposition, particularly during the inflammation stage. Transcriptomic analysis revealed significant overlap, but differences were observed and clarified in Gene Ontology and KEGG pathway analysis, potentially influenced by changes in interferon-gamma-mediated lipid metabolism. This suggests the suitability of 65 Gy for future preclinical basic and pharmaceutical research connected with radiation-induced lung injury.<\/jats:p>","DOI":"10.3390\/ijms25073766","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T12:52:12Z","timestamp":1711630332000},"page":"3766","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Transcriptional Changes in Radiation-Induced Lung Injury: A Comparative Analysis of Two Radiation Doses for Preclinical Research"],"prefix":"10.3390","volume":"25","author":[{"given":"Mohamed El-Agamy","family":"Farh","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"},{"name":"Drug Development Team, ARONTIER, Co., Ltd., Seoul 06735, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9742-0508","authenticated-orcid":false,"given":"Hyun-Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9486-4122","authenticated-orcid":false,"given":"Sang-Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajeong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronglan","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soorim","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5819-9783","authenticated-orcid":false,"given":"Dong Wook","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunjoo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon-Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Korea Institute of Radiological and Medical Science, Seoul 01812, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7538-8850","authenticated-orcid":false,"given":"Yun-Sil","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Science, Ewha Womans University, Seoul 03760, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Insuk","family":"Sohn","sequence":"additional","affiliation":[{"name":"Drug Development Team, ARONTIER, Co., Ltd., Seoul 06735, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9966-5157","authenticated-orcid":false,"given":"Jaeho","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/j.ijrobp.2006.01.051","article-title":"Final Toxicity Results of a Radiation-Dose Escalation Study in Patients with Non\u2013Small-Cell Lung Cancer (NSCLC): Predictors for Radiation Pneumonitis and Fibrosis","volume":"65","author":"Kong","year":"2006","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"90579","DOI":"10.18632\/oncotarget.21234","article-title":"Interactions between TGF-\u03921, Canonical WNT\/\u03b2-Catenin Pathway and PPAR \u03b3 in Radiation-Induced Fibrosis","volume":"8","author":"Lecarpentier","year":"2017","journal-title":"Oncotarget"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1007\/s00432-015-1974-6","article-title":"Radiation-Induced Fibrosis: Mechanisms and Implications for Therapy","volume":"141","author":"Straub","year":"2015","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.trsl.2021.06.002","article-title":"Involvement of ENAMPT\/TLR4 Signaling in Murine Radiation Pneumonitis: Protection by ENAMPT Neutralization","volume":"239","author":"Garcia","year":"2022","journal-title":"Transl. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1080\/01902148.2017.1318975","article-title":"Radiation Induced Pulmonary Fibrosis as a Model of Progressive Fibrosis: Contributions of DNA Damage, Inflammatory Response and Cellular Senescence Genes","volume":"43","author":"Beach","year":"2017","journal-title":"Exp. Lung Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s00109-018-1715-9","article-title":"Identification of Molecular Signatures Involved in Radiation-Induced Lung Fibrosis","volume":"97","author":"Jin","year":"2019","journal-title":"J. Mol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/s41419-020-02846-7","article-title":"LXA4-FPR2 Signaling Regulates Radiation-Induced Pulmonary Fibrosis via Crosstalk with TGF-\u03b2\/Smad Signaling","volume":"11","author":"Kim","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/gt.2016.86","article-title":"Adenovirus-Mediated Foxp3 Expression in Lung Epithelial Cells Ameliorates Acute Radiation-Induced Pneumonitis in Mice","volume":"24","author":"Shin","year":"2017","journal-title":"Gene Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1559325819891012","article-title":"Identification of LncRNA, MicroRNA, and MRNA-Associated CeRNA Network of Radiation-Induced Lung Injury in a Mice Model","volume":"17","author":"Li","year":"2019","journal-title":"Dose Response"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"19701","DOI":"10.1038\/s41598-019-56027-4","article-title":"Transcriptome Alteration Spectrum in Rat Lung Induced by Radiotherapy","volume":"9","author":"Zhang","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.ijrobp.2021.03.058","article-title":"Clinicopathologic and Transcriptomic Analysis of Radiation-Induced Lung Injury in Nonhuman Primates","volume":"111","author":"Thakur","year":"2021","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Liu, X., Shao, C., and Fu, J. (2021). Promising Biomarkers of Radiation-Induced Lung Injury: A Review. Biomedicines, 9.","DOI":"10.3390\/biomedicines9091181"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/cei.13253","article-title":"Secretory Immunoglobulin A Induces Human Lung Fibroblasts to Produce Inflammatory Cytokines and Undergo Activation","volume":"195","author":"Arakawa","year":"2019","journal-title":"Clin. Exp. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"45001","DOI":"10.1038\/srep45001","article-title":"Standardized Herbal Formula PM014 Inhibits Radiation-Induced Pulmonary Inflammation in Mice","volume":"7","author":"Kim","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s00408-015-9825-4","article-title":"Time, Dose, and Volume Responses in a Mouse Pulmonary Injury Model Following Ablative Irradiation","volume":"194","author":"Hong","year":"2016","journal-title":"Lung"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1165\/rcmb.2014-0343OC","article-title":"A Pneumocyte-Macrophage Paracrine Lipid Axis Drives the Lung toward Fibrosis","volume":"53","author":"Romero","year":"2015","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1378\/chest.08-0306","article-title":"Eicosanoid Lipid Mediators in Fibrotic Lung Diseases: Ready for Prime Time?","volume":"133","author":"Huang","year":"2008","journal-title":"Chest"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/j.jaci.2019.11.032","article-title":"Inhibiting Eicosanoid Degradation Exerts Antifibrotic Effects in a Pulmonary Fibrosis Mouse Model and Human Tissue","volume":"145","author":"Theiler","year":"2020","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"794629","DOI":"10.3389\/fphys.2021.794629","article-title":"Fatty Acid Metabolism and Idiopathic Pulmonary Fibrosis","volume":"12","author":"Geng","year":"2022","journal-title":"Front. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3446","DOI":"10.12659\/MSM.902353","article-title":"The Cellular and Molecular Mechanism of Radiation-Induced Lung Injury","volume":"23","author":"Huang","year":"2017","journal-title":"Med. Sci. Monit."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"136","DOI":"10.4103\/ijpvm.IJPVM_193_20","article-title":"Adiponectin: Role in Physiology and Pathophysiology","volume":"11","author":"Nguyen","year":"2020","journal-title":"Int. J. Prev. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1165\/rcmb.2005-0359OC","article-title":"Respiratory Epithelial Gene Expression in Patients with Mild and Severe Cystic Fibrosis Lung Disease","volume":"35","author":"Wright","year":"2006","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.mehy.2018.12.005","article-title":"Adiponectin: A Potential Candidate for Treating Fibrosis in Posterior Segment of the Eye","volume":"123","author":"Palanisamy","year":"2019","journal-title":"Med. Hypotheses"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Yao, R., Cao, Y., He, Y.R., Lau, W.B., Zeng, Z., and Liang, Z.A. (2015). Adiponectin Attenuates Lung Fibroblasts Activation and Pulmonary Fibrosis Induced by Paraquat. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125169"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"478580","DOI":"10.3389\/fimmu.2019.02555","article-title":"Adiponectin Limits IFN-\u03b3 and Il-17 Producing CD4 T Cells in Obesity by Restraining Cell Intrinsic Glycolysis","volume":"10","author":"Surendar","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/B978-0-12-800141-7.00004-8","article-title":"Metabolic Syndrome in Pediatrics","volume":"65","author":"Kursawe","year":"2014","journal-title":"Adv. Clin. Chem."},{"key":"ref_27","unstructured":"Chabowski, A., and G\u00f3rski, J. (2018). Muscle and Exercise Physiology, Academic Press."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1111\/resp.13981","article-title":"Long-Chain Fatty Acids Are Bad in IPF, or Are They?","volume":"26","author":"McManus","year":"2021","journal-title":"Respirology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1111\/exd.14181","article-title":"Dermal Adipocytes Contribute to the Metabolic Regulation of Dermal Fibroblasts","volume":"30","author":"Zhang","year":"2021","journal-title":"Exp. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"13974","DOI":"10.1074\/jbc.RA118.003541","article-title":"Perilipin 1 (Plin1) Deficiency Promotes Inflammatory Responses in Lean Adipose Tissue through Lipid Dysregulation","volume":"293","author":"Sohn","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"654.11","DOI":"10.1096\/fasebj.2019.33.1_supplement.654.11","article-title":"Effect of Interferon Gamma on Neutral Lipid Levels, Lipid Droplet Formation, and Antiviral Responses in Pancreatic Islets and INS-1 \u03b2 Cells","volume":"33","author":"Truong","year":"2019","journal-title":"FASEB J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"16112","DOI":"10.1038\/s41598-020-72629-9","article-title":"PM014 Attenuates Radiation-Induced Pulmonary Fibrosis via Regulating NF-KB and TGF-B1\/NOX4 Pathways","volume":"10","author":"Park","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7967868","DOI":"10.1155\/2018\/7967868","article-title":"Serotonin Exhibits Accelerated Bleomycin-Induced Pulmonary Fibrosis through TPH1 Knockout Mouse Experiments","volume":"2018","author":"Zhang","year":"2018","journal-title":"Mediators Inflamm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1136\/jcp.41.4.467","article-title":"Simple Method of Estimating Severity of Pulmonary Fibrosis on a Numerical Scale","volume":"41","author":"Ashcroft","year":"1988","journal-title":"J. Clin. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"507","DOI":"10.2144\/000112729","article-title":"Standardized Quantification of Pulmonary Fibrosis in Histological Samples","volume":"44","author":"Gitter","year":"2008","journal-title":"Biotechniques"},{"key":"ref_36","first-page":"14904","article-title":"A Convenient Method for Quantifying Collagen Fibers in Atherosclerotic Lesions by Imagej Software","volume":"10","author":"Chen","year":"2017","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Robinson, M.D., McCarthy, D.J., and Smyth, G.K. (2010). EdgeR: A Bioconductor Package for Differential Expression Analysis of Digital Gene Expression Data. Bioinformatics, 26.","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R Stat. Soc. Ser. B Methodol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Rohart, F., Gautier, B., Singh, A., and L\u00ea Cao, K.A. (2017). MixOmics: An R Package for \u2018omics Feature Selection and Multiple Data Integration. PLoS Comput. Biol., 13.","DOI":"10.1101\/108597"},{"key":"ref_40","unstructured":"Warnes, G.R., Bolker, B., Bonebakker, L., Gentleman, R., Liaw, W.H.A., Lumley, T., Maechler, M., Magnusson, A., Moeller, S., and Schwartz, M. (2023, February 01). Gplots: Various R Programming Tools for Plotting Data. R Package Version 3.0.1.1. Available online: http:\/\/CRAN.R-project.org\/package=gplots."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Chen, H., and Boutros, P.C. (2011). VennDiagram: A Package for the Generation of Highly-Customizable Venn and Euler Diagrams in R. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-35"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.chom.2015.11.002","article-title":"Meta- and Orthogonal Integration of Influenza \u201cOMICs\u201d Data Defines a Role for UBR4 in Virus Budding","volume":"18","author":"Tripathi","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"D559","DOI":"10.1093\/nar\/gky973","article-title":"CORUM: The Comprehensive Resource of Mammalian Protein Complexes\u20142019","volume":"47","author":"Giurgiu","year":"2019","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/7\/3766\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:19:58Z","timestamp":1760105998000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/7\/3766"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,28]]},"references-count":43,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["ijms25073766"],"URL":"https:\/\/doi.org\/10.3390\/ijms25073766","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,28]]}}}