{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T15:11:16Z","timestamp":1774451476922,"version":"3.50.1"},"reference-count":54,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP20K08560"],"award-info":[{"award-number":["JP20K08560"]}]},{"name":"JSPS KAKENHI","award":["JP23K15182"],"award-info":[{"award-number":["JP23K15182"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by irreversible fibrosis. Aberrant cell differentiation plays a crucial role in the development of IPF. Although recent studies have suggested that mitochondrial dysfunction may play a role in IPF, its direct impact on fibrosis remains unclear. This study aimed to clarify the role of mitochondria in lung cell differentiation and pulmonary fibrosis development by employing mito-mice ND6M, in which the activity of respiratory chain complex I is decreased due to a mitochondrial DNA mutation (G13997A). Pulmonary fibrosis was induced by administering bleomycin (BLM) to both wild-type and mito-mice ND6M. Bone marrow-derived macrophages and primary lung fibroblasts, generated from both types of mice, were analyzed to evaluate M1\/M2 polarization and myofibroblast differentiation, respectively. Compared to wild-type mice, mito-mice ND6M exhibited more severe fibrosis and lower survival rates following BLM inoculation. Lactate production in the lungs after BLM administration was significantly higher in mito-mice ND6M than in wild-type mice. TGF-\u03b21-treated fibroblasts from mito-mice ND6M exhibited increased \u03b1-smooth muscle actin expression. While type I collagen expression was not different between these mice, TGF-\u03b21-induced expression of phosphoserine phosphatase and serine hydroxymethyltransferase2, two of the enzymes involved in the serine\u2013glycine pathway, was significantly higher in mito-mice ND6M than in wild-type mice. On the other hand, mitochondrial dysfunction had a small effect on pulmonary inflammation and on M1\/M2 macrophage polarization. In conclusion, mitochondrial dysfunction promotes TGF-\u03b21-induced myofibroblast differentiation and BLM-induced pulmonary fibrosis. Mitochondria-dependent metabolic reprogramming may therefore represent a promising therapeutic target in IPF.<\/jats:p>","DOI":"10.3390\/cells15070582","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T13:57:34Z","timestamp":1774447054000},"page":"582","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondria-Dependent Metabolic Reprogramming Enhances Myofibroblast Differentiation and Aggravates Bleomycin-Induced Pulmonary Fibrosis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6566-6140","authenticated-orcid":false,"given":"Kai","family":"Yazaki","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, Institute of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosuke","family":"Matsuno","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Nikko Memorial Hospital, Hitachi 317-0055, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Yabuuchi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Institute of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sosuke","family":"Matsumura","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Institute of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenya","family":"Kuramoto","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Institute of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazufumi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Institute of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8880-6951","authenticated-orcid":false,"given":"Masashi","family":"Matsuyama","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Institute of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3918-9878","authenticated-orcid":false,"given":"Takumi","family":"Kiwamoto","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Institute of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7407-4243","authenticated-orcid":false,"given":"Yuko","family":"Morishima","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Institute of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukio","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, National Hospital Organization Ibarakihigashi National Hospital, Tokai 319-1113, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaori","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Institute of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuto","family":"Nakada","sequence":"additional","affiliation":[{"name":"Institute of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1822-2448","authenticated-orcid":false,"given":"Nobuyuki","family":"Hizawa","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Institute of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e18","DOI":"10.1164\/rccm.202202-0399ST","article-title":"Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS\/ERS\/JRS\/ALAT Clinical Practice Guideline","volume":"205","author":"Raghu","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12931-018-0730-2","article-title":"Idiopathic pulmonary fibrosis: Pathogenesis and management","volume":"19","author":"Sgalla","year":"2018","journal-title":"Respir. Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Pokhreal, D., Crestani, B., and Helou, D.G. (2023). Macrophage Implication in IPF: Updates on Immune, Epigenetic, and Metabolic Pathways. Cells, 12.","DOI":"10.3390\/cells12172193"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1172\/JCI87440","article-title":"Mitochondria in the spotlight of aging and idiopathic pulmonary fibrosis","volume":"127","author":"Mora","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Cala-Garcia, J.D., Medina-Rincon, G.J., Sierra-Salas, P.A., Rojano, J., and Romero, F. (2023). The Role of Mitochondrial Dysfunction in Idiopathic Pulmonary Fibrosis: New Perspectives for a Challenging Disease. Biology, 12.","DOI":"10.3390\/biology12091237"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/j.1476-5381.2011.01247.x","article-title":"Novel therapeutic approaches for pulmonary fibrosis","volume":"163","author":"Datta","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1172\/JCI74942","article-title":"PINK1 deficiency impairs mitochondrial homeostasis and promotes lung fibrosis","volume":"125","author":"Bueno","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1164\/rccm.201201-0084OC","article-title":"Lactic acid is elevated in idiopathic pulmonary fibrosis and induces myofibroblast differentiation via pH-dependent activation of transforming growth factor-\u03b2","volume":"186","author":"Kottmann","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/ni.2956","article-title":"Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages","volume":"15","author":"Huang","year":"2014","journal-title":"Nat. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1038\/nm.2005","article-title":"NADPH oxidase-4 mediates myofibroblast activation and fibrogenic responses to lung injury","volume":"15","author":"Hecker","year":"2009","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1136\/thx.2009.113456","article-title":"NOX4\/NADPH oxidase expression is increased in pulmonary fibroblasts from patients with idiopathic pulmonary fibrosis and mediates TGFbeta1-induced fibroblast differentiation into myofibroblasts","volume":"65","author":"Amara","year":"2010","journal-title":"Thorax"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"151181","DOI":"10.1016\/j.ejcb.2021.151181","article-title":"ROS-Nrf2 pathway mediates the development of TGF-\u03b21-induced epithelial-mesenchymal transition through the activation of Notch signaling","volume":"100","author":"Yazaki","year":"2021","journal-title":"Eur. J. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/j.bbabio.2010.02.011","article-title":"Hypoxia and mitochondrial oxidative metabolism","volume":"1797","author":"Solaini","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"129835","DOI":"10.1016\/j.bbagen.2020.129835","article-title":"Attempts to understand the mechanisms of mitochondrial diseases: The reverse genetics of mouse models for mitochondrial disease","volume":"1865","author":"Ishikawa","year":"2021","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1146\/annurev.pathol.4.110807.092314","article-title":"Mitochondrial energetics and therapeutics","volume":"5","author":"Wallace","year":"2010","journal-title":"Annu. Rev. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10528","DOI":"10.1073\/pnas.1202367109","article-title":"Specific mitochondrial DNA mutation in mice regulates diabetes and lymphoma development","volume":"109","author":"Hashizume","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3525","DOI":"10.1016\/j.febslet.2008.09.024","article-title":"Enhanced glycolysis induced by mtDNA mutations does not regulate metastasis","volume":"582","author":"Ishikawa","year":"2008","journal-title":"FEBS Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3943","DOI":"10.1016\/j.febslet.2010.07.048","article-title":"Generation of trans-mitochondrial mito-mice by the introduction of a pathogenic G13997A mtDNA from highly metastatic lung carcinoma cells","volume":"584","author":"Yokota","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Egger, C., Cannet, C., G\u00e9rard, C., Jarman, E., Jarai, G., Feige, A., Suply, T., Micard, A., Dunbar, A., and Tigani, B. (2013). Administration of bleomycin via the oropharyngeal aspiration route leads to sustained lung fibrosis in mice and rats as quantified by UTE-MRI and histology. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063432"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1046\/j.1365-2613.2002.00220.x","article-title":"Time course of bleomycin-induced lung fibrosis","volume":"83","author":"Izbicki","year":"2002","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"L313","DOI":"10.1152\/ajplung.00434.2002","article-title":"Induction of arginase I and II in bleomycin-induced fibrosis of mouse lung","volume":"285","author":"Endo","year":"2003","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"101509","DOI":"10.1016\/j.redox.2020.101509","article-title":"Mitochondria dysfunction and metabolic reprogramming as drivers of idiopathic pulmonary fibrosis","volume":"33","author":"Bueno","year":"2020","journal-title":"Redox Biol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Patel, A.S., Song, J.W., Chu, S.G., Mizumura, K., Osorio, J.C., Shi, Y., El-Chemaly, S., Lee, C.G., Rosas, I.O., and Elias, J.A. (2015). Epithelial cell mitochondrial dysfunction and PINK1 are induced by transforming growth factor-beta1 in pulmonary fibrosis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0121246"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1096\/fj.201601077R","article-title":"SIRT3 deficiency promotes lung fibrosis by augmenting alveolar epithelial cell mitochondrial DNA damage and apoptosis","volume":"31","author":"Jablonski","year":"2017","journal-title":"FASEB J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1038\/s41586-023-06423-8","article-title":"Mitochondrial integrated stress response controls lung epithelial cell fate","volume":"620","author":"Han","year":"2023","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"100241","DOI":"10.1016\/j.mocell.2025.100241","article-title":"Building blocks for lung regeneration: Stem cells and niches","volume":"48","author":"Lee","year":"2025","journal-title":"Mol. Cells"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1164\/rccm.201504-0780OC","article-title":"Glycolytic Reprogramming in Myofibroblast Differentiation and Lung Fibrosis","volume":"192","author":"Xie","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3733","DOI":"10.1096\/fj.201600428R","article-title":"Profibrotic up-regulation of glucose transporter 1 by TGF-\u03b2 involves activation of MEK and mammalian target of rapamycin complex 2 pathways","volume":"30","author":"Andrianifahanana","year":"2016","journal-title":"FASEB J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1165\/rcmb.2016-0225OC","article-title":"Glucose Transporter 1-Dependent Glycolysis Is Increased during Aging-Related Lung Fibrosis, and Phloretin Inhibits Lung Fibrosis","volume":"56","author":"Cho","year":"2017","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"L1164","DOI":"10.1152\/ajplung.00220.2017","article-title":"IPF lung fibroblasts have a senescent phenotype","volume":"313","author":"Bueno","year":"2017","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1165\/rcmb.2016-0186OC","article-title":"Targeting Hypoxia-Inducible Factor-1\u03b1\/Pyruvate Dehydrogenase Kinase 1 Axis by Dichloroacetate Suppresses Bleomycin-induced Pulmonary Fibrosis","volume":"58","author":"Goodwin","year":"2018","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"25427","DOI":"10.1074\/jbc.M115.646984","article-title":"Metabolic Reprogramming Is Required for Myofibroblast Contractility and Differentiation","volume":"290","author":"Bernard","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"eaav3048","DOI":"10.1126\/scisignal.aav3048","article-title":"mTORC1 amplifies the ATF4-dependent de novo serine-glycine pathway to supply glycine during TGF-\u03b2(1)-induced collagen biosynthesis","volume":"12","author":"Selvarajah","year":"2019","journal-title":"Sci. Signal."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1165\/rcmb.2017-0186OC","article-title":"Inhibition of Phosphoglycerate Dehydrogenase Attenuates Bleomycin-induced Pulmonary Fibrosis","volume":"58","author":"Hamanaka","year":"2018","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9250","DOI":"10.1038\/s41467-025-64320-2","article-title":"Mitochondrial one-carbon metabolism is required for TGF-\u03b2-induced glycine synthesis and fibrotic responses","volume":"16","author":"Meliton","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1007\/s10528-025-11071-w","article-title":"Decreased Complex I Activity in Blood lymphocytes Correlates with Idiopathic Pulmonary Fibrosis Severity","volume":"64","author":"Zifa","year":"2026","journal-title":"Biochem. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4848","DOI":"10.1093\/emboj\/17.16.4848","article-title":"The mtDNA-encoded ND6 subunit of mitochondrial NADH dehydrogenase is essential for the assembly of the membrane arm and the respiratory function of the enzyme","volume":"17","author":"Bai","year":"1998","journal-title":"EMBO J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"10925","DOI":"10.1038\/s41598-025-91746-x","article-title":"Characterization of a new mutation of mitochondrial ND6 gene in hepatocellular carcinoma and its effects on respiratory complex I","volume":"15","author":"Bazzani","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"L1305","DOI":"10.1152\/ajplung.00058.2015","article-title":"Pharmacologic inhibition of lactate production prevents myofibroblast differentiation","volume":"309","author":"Kottmann","year":"2015","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"mjae021","DOI":"10.1093\/jmcb\/mjae021","article-title":"CCT6A alleviates pulmonary fibrosis by inhibiting HIF-1\u03b1-mediated lactate production","volume":"16","author":"Yan","year":"2024","journal-title":"J. Mol. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/s41392-024-01764-w","article-title":"TGF-\u03b2 signaling in health, disease, and therapeutics","volume":"9","author":"Deng","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.cellimm.2018.01.009","article-title":"Metabolic regulation of macrophages in tissues","volume":"330","author":"Saraber","year":"2018","journal-title":"Cell. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ball, A.B., Jones, A.E., Nguy, K.B., Rios, A., Marx, N., Hsieh, W.Y., Yang, K., Desousa, B.R., Kim, K.K.O., and Veliova, M. (2024). Pro-inflammatory macrophage activation does not require inhibition of mitochondrial respiration. bioRxiv.","DOI":"10.1101\/2024.05.10.593451"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.celrep.2016.09.008","article-title":"Mitochondrial Dysfunction Prevents Repolarization of Inflammatory Macrophages","volume":"17","author":"Baardman","year":"2016","journal-title":"Cell Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6082","DOI":"10.4049\/jimmunol.1402469","article-title":"Pyruvate dehydrogenase kinase 1 participates in macrophage polarization via regulating glucose metabolism","volume":"194","author":"Tan","year":"2015","journal-title":"J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e11612","DOI":"10.7554\/eLife.11612","article-title":"Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation","volume":"5","author":"Covarrubias","year":"2016","journal-title":"eLife"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1186\/s12931-019-1196-6","article-title":"Accumulation of damaged mitochondria in alveolar macrophages with reduced OXPHOS related gene expression in IPF","volume":"20","author":"Tsitoura","year":"2019","journal-title":"Respir. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"L834","DOI":"10.1152\/ajplung.00235.2017","article-title":"Metabolic characterization and RNA profiling reveal glycolytic dependence of profibrotic phenotype of alveolar macrophages in lung fibrosis","volume":"313","author":"Xie","year":"2017","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1378\/chest.07-1948","article-title":"Baseline BAL neutrophilia predicts early mortality in idiopathic pulmonary fibrosis","volume":"133","author":"Kinder","year":"2008","journal-title":"Chest"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e001202","DOI":"10.1136\/bmjresp-2022-001202","article-title":"Neutrophil lymphocyte ratio as an indicator for disease progression in Idiopathic Pulmonary Fibrosis","volume":"9","author":"Achaiah","year":"2022","journal-title":"BMJ Open Respir. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e125937","DOI":"10.1172\/jci.insight.125937","article-title":"FPR-1 is an important regulator of neutrophil recruitment and a tissue-specific driver of pulmonary fibrosis","volume":"5","author":"Leslie","year":"2020","journal-title":"JCI Insight"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s00109-020-02001-x","article-title":"The heterodimer S100A8\/A9 is a potent therapeutic target for idiopathic pulmonary fibrosis","volume":"99","author":"Araki","year":"2021","journal-title":"J. Mol. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1002\/path.4359","article-title":"Neutrophil extracellular traps promote differentiation and function of fibroblasts","volume":"233","author":"Chrysanthopoulou","year":"2014","journal-title":"J. Pathol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/7\/582\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T14:11:06Z","timestamp":1774447866000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/7\/582"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,25]]},"references-count":54,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["cells15070582"],"URL":"https:\/\/doi.org\/10.3390\/cells15070582","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,25]]}}}