{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:44:50Z","timestamp":1785437090294,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,30]]},"group-title":"Pathology","reference-count":83,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["S10OD028483"],"award-info":[{"award-number":["S10OD028483"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["S10OD016236"],"award-info":[{"award-number":["S10OD016236"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["U54AG075931"],"award-info":[{"award-number":["U54AG075931"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P50AR080612"],"award-info":[{"award-number":["P50AR080612"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01HL146519"],"award-info":[{"award-number":["R01HL146519"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["512453064"],"award-info":[{"award-number":["512453064"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"publisher"}]},{"award":["54210281"],"award-info":[{"award-number":["54210281"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Hessisches Ministerium f\u00fcr Wissenschaft und Forschung, Kunst und Kultur","award":["LOEWE Habitat"],"award-info":[{"award-number":["LOEWE Habitat"]}]},{"DOI":"10.13039\/501100010564","name":"German Center for Lung Research","doi-asserted-by":"crossref","award":["DZL"],"award-info":[{"award-number":["DZL"]}],"id":[{"id":"10.13039\/501100010564","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"crossref","award":["Career Award for Medical Scientists"],"award-info":[{"award-number":["Career Award for Medical Scientists"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100017650","name":"Three Lakes Foundation","doi-asserted-by":"crossref","award":["Three Lakes Foundation"],"award-info":[{"award-number":["Three Lakes Foundation"]}],"id":[{"id":"10.13039\/100017650","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,18]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Idiopathic pulmonary fibrosis (IPF) is characterized by failed alveolar epithelial repair and progressive fibrotic remodeling. Although aberrant reprogramming of alveolar type 2 (AT2) cells and accumulation of transitional AT2 states are increasing recognized as central features of IPF, the epithelial-intrinsic mechanisms that initiate these pathogenic states remain incompletely understood. Here, we identify mitochondrial transcription factor A (TFAM), a regulator of mitochondrial DNA maintenance, as a critical regulator of AT2 cell homeostasis. TFAM expression was reduced in AT2 cells from human IPF lungs. Inducible AT2 cell-specific\n                  <jats:italic>Tfam<\/jats:italic>\n                  deletion in mice caused spontaneous fibrotic remodeling and increased susceptibility to bleomycin-induced lung injury. TFAM-deficient AT2 cells acquired KRT8\n                  <jats:sup>+<\/jats:sup>\n                  transitional and p21\n                  <jats:sup>+<\/jats:sup>\n                  senescence-associated features before the onset of fibrotic transformation, accompanied by impaired oxidative phosphorylation, redox imbalance, mitochondrial superoxide accumulation, repression of mtDNA-encoded respiratory genes, and disrupted mitochondrial ultrastructure. TFAM-deficient AT2 cells developed a profibrotic secretory program that promoted extracellular matrix deposition and fibroblast activation. We further identified insulin-like growth factor-binding protein 2 (IGFBP2) as a secreted mediator induced in TFAM-deficient AT2 cells. IGFBP2 was elevated in AT2 cells in human IPF lung tissue and bronchoalveolar lavage fluid (BALF) from patients with IPF. IGFBP2 was detected in supernatants from fibrotic human precision-cut lung slices (hPCLS). IGFBP2 neutralization attenuated profibrotic remodeling in fibrotic hPCLS. Collectively, our findings identify TFAM-dependent mitochondrial homeostasis as an epithelial checkpoint linking AT2 cell-state stability to impaired epithelial-mesenchymal crosstalk driving pulmonary fibrosis.\n                <\/jats:p>","DOI":"10.64898\/2026.05.28.728065","type":"posted-content","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T20:10:53Z","timestamp":1780171853000},"source":"Crossref","is-referenced-by-count":0,"title":["Alveolar Epithelial Cell Loss of the Mitochondrial Regulator TFAM Drives Progressive Lung Fibrosis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1069-3181","authenticated-orcid":false,"given":"Qianjiang","family":"Hu","sequence":"first","affiliation":[{"name":"Center of Lung Aging and Regeneration, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugochi","family":"Onwuka","sequence":"additional","affiliation":[{"name":"Center of Lung Aging and Regeneration, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayra","family":"Cardenes","sequence":"additional","affiliation":[{"name":"Center of Lung Aging and Regeneration, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline","family":"Packwood","sequence":"additional","affiliation":[{"name":"Center of Lung Aging and Regeneration, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen L.","family":"Huang","sequence":"additional","affiliation":[{"name":"Center of Lung Aging and Regeneration, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Shi","sequence":"additional","affiliation":[{"name":"Center of Lung Aging and Regeneration, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Camila","family":"Melo-Narvaez","sequence":"additional","affiliation":[{"name":"Institute for Lung Research, Philipps-University Marburg, Member of the German Center for Lung Research (DZL), Marburg, Germany"},{"name":"Institute of Lung Health and Immunity (LHI) and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Munich, Member of the German Center for Lung Research (DZL), Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puja","family":"Dutta","sequence":"additional","affiliation":[{"name":"Center of Lung Aging and Regeneration, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihe","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center of Lung Aging and Regeneration, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Beaulieu","sequence":"additional","affiliation":[{"name":"Center of Lung Aging and Regeneration, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byron","family":"Chuan","sequence":"additional","affiliation":[{"name":"Center of Lung Aging and Regeneration, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavan","family":"Suresh","sequence":"additional","affiliation":[{"name":"Center of Lung Aging and Regeneration, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin Michael","family":"Redding","sequence":"additional","affiliation":[{"name":"Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA"},{"name":"Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, USA"},{"name":"Division of Cardiology, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura-Marie","family":"Twardowski","sequence":"additional","affiliation":[{"name":"Institute for Lung Research, Philipps-University Marburg, Member of the German Center for Lung Research (DZL), Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scarlett","family":"Varley","sequence":"additional","affiliation":[{"name":"Center of Lung Aging and Regeneration, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo H.","family":"Pineda","sequence":"additional","affiliation":[{"name":"Center of Lung Aging and Regeneration, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Sembrat","sequence":"additional","affiliation":[{"name":"Center of Lung Aging and Regeneration, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara Lisa Grove","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Franks","sequence":"additional","affiliation":[{"name":"Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon C.","family":"Watkins","sequence":"additional","affiliation":[{"name":"Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudette St.","family":"Croix","sequence":"additional","affiliation":[{"name":"Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3815-9370","authenticated-orcid":false,"given":"Corrine R.","family":"Kliment","sequence":"additional","affiliation":[{"name":"Center of Lung Aging and Regeneration, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Eickelberg","sequence":"additional","affiliation":[{"name":"Center of Lung Aging and Regeneration, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mareike","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Institute for Lung Research, Philipps-University Marburg, Member of the German Center for Lung Research (DZL), Marburg, Germany"},{"name":"Institute of Lung Health and Immunity (LHI) and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Munich, Member of the German Center for Lung Research (DZL), Munich, Germany"},{"name":"Institute for Lung Health (ILH), Member of the German Center for Lung Research (DZL), and Cardiopulmonary Institute (CPI), Justus-Liebig University Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Bueno","sequence":"additional","affiliation":[{"name":"Center of Lung Aging and Regeneration, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4767-4937","authenticated-orcid":false,"given":"Brett A.","family":"Kaufman","sequence":"additional","affiliation":[{"name":"Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA"},{"name":"Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, USA"},{"name":"Division of Cardiology, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"K\u00f6nigshoff","sequence":"additional","affiliation":[{"name":"Center of Lung Aging and Regeneration, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"},{"name":"Geriatric Research Education and Clinical Center (GRECC) at the VA Pittsburgh Healthcare System, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026072217151648000_2026.05.28.728065v2.1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(11)60052-4"},{"key":"2026072217151648000_2026.05.28.728065v2.2","doi-asserted-by":"crossref","first-page":"17074","DOI":"10.1038\/nrdp.2017.74","article-title":"Idiopathic pulmonary fibrosis","volume":"3","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"2026072217151648000_2026.05.28.728065v2.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1705751"},{"key":"2026072217151648000_2026.05.28.728065v2.4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-042320-030240"},{"issue":"1","key":"2026072217151648000_2026.05.28.728065v2.5","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1146\/annurev-med-050224-121458","article-title":"Diffuse Parenchymal Lung Disease: Updates in Pathophysiology and Management","volume":"77","year":"2026","journal-title":"Annu Rev Med"},{"key":"2026072217151648000_2026.05.28.728065v2.6","doi-asserted-by":"publisher","DOI":"10.1172\/JCI68782"},{"key":"2026072217151648000_2026.05.28.728065v2.7","doi-asserted-by":"publisher","DOI":"10.1038\/nature12930"},{"key":"2026072217151648000_2026.05.28.728065v2.8","doi-asserted-by":"publisher","DOI":"10.1164\/RCCM.201712-2410OC\/SUPPL_FILE\/DISCLOSURES.PDF"},{"key":"2026072217151648000_2026.05.28.728065v2.9","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba1983"},{"key":"2026072217151648000_2026.05.28.728065v2.10","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba1972"},{"key":"2026072217151648000_2026.05.28.728065v2.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-63735-1"},{"issue":"5","key":"2026072217151648000_2026.05.28.728065v2.12","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1165\/rcmb.2024-0372TR","article-title":"From Epithelium to Therapy: Transitional Cells in Lung Fibrosis","volume":"72","year":"2025","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026072217151648000_2026.05.28.728065v2.13","doi-asserted-by":"crossref","unstructured":"Wang F , et al. Regulation of epithelial transitional states in murine and human pulmonary fibrosis. J Clin Invest. 2023;133(22).","DOI":"10.1172\/JCI165612"},{"key":"2026072217151648000_2026.05.28.728065v2.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17358-3"},{"key":"2026072217151648000_2026.05.28.728065v2.15","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201909-1726LE"},{"key":"2026072217151648000_2026.05.28.728065v2.16","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4447"},{"issue":"6","key":"2026072217151648000_2026.05.28.728065v2.17","doi-asserted-by":"crossref","first-page":"e0218003","DOI":"10.1371\/journal.pone.0218003","article-title":"PINK1 attenuates mtDNA release in alveolar epithelial cells and TLR9 mediated profibrotic responses","volume":"14","year":"2019","journal-title":"PLOS ONE"},{"key":"2026072217151648000_2026.05.28.728065v2.18","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74942"},{"key":"2026072217151648000_2026.05.28.728065v2.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.11.011"},{"key":"2026072217151648000_2026.05.28.728065v2.20","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2022-0315OC"},{"key":"2026072217151648000_2026.05.28.728065v2.21","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E07-05-0404"},{"key":"2026072217151648000_2026.05.28.728065v2.22","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2003638"},{"key":"2026072217151648000_2026.05.28.728065v2.23","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh109"},{"key":"2026072217151648000_2026.05.28.728065v2.24","doi-asserted-by":"publisher","DOI":"10.1038\/ng0398-231"},{"key":"2026072217151648000_2026.05.28.728065v2.25","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4077"},{"key":"2026072217151648000_2026.05.28.728065v2.26","doi-asserted-by":"publisher","DOI":"10.1038\/nature14156"},{"issue":"12","key":"2026072217151648000_2026.05.28.728065v2.27","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1038\/s42255-019-0150-8","article-title":"Mitochondrial DNA Stress Signalling Protects the Nuclear Genome","volume":"1","year":"2019","journal-title":"Nat Metab"},{"issue":"5","key":"2026072217151648000_2026.05.28.728065v2.28","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1002\/art.42033","article-title":"Impaired Mitochondrial Transcription Factor A Expression Promotes Mitochondrial Damage to Drive Fibroblast Activation and Fibrosis in Systemic Sclerosis","volume":"74","year":"2022","journal-title":"Arthritis Rheumatol"},{"key":"2026072217151648000_2026.05.28.728065v2.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.08.003"},{"key":"2026072217151648000_2026.05.28.728065v2.30","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06423-8"},{"key":"2026072217151648000_2026.05.28.728065v2.31","doi-asserted-by":"crossref","unstructured":"Bueno M , et al. CYB5R3 in type II alveolar epithelial cells protects against lung fibrosis by suppressing TGF-\u03b21 signaling. JCI Insight. 2023;8(5).","DOI":"10.1172\/jci.insight.161487"},{"key":"2026072217151648000_2026.05.28.728065v2.32","doi-asserted-by":"crossref","unstructured":"Angeles-Lopez QD , et al. Regulation of lung progenitor plasticity and repair by fatty acid oxidation. JCI Insight. 2025;10(3).","DOI":"10.1172\/jci.insight.165837"},{"key":"2026072217151648000_2026.05.28.728065v2.33","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-015-2170-4"},{"key":"2026072217151648000_2026.05.28.728065v2.34","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00186914"},{"key":"2026072217151648000_2026.05.28.728065v2.35","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32552-1"},{"key":"2026072217151648000_2026.05.28.728065v2.36","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp073"},{"key":"2026072217151648000_2026.05.28.728065v2.37","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1011"},{"key":"2026072217151648000_2026.05.28.728065v2.38","doi-asserted-by":"publisher","DOI":"10.1038\/srep20547"},{"key":"2026072217151648000_2026.05.28.728065v2.39","doi-asserted-by":"publisher","DOI":"10.1172\/jci33950"},{"key":"2026072217151648000_2026.05.28.728065v2.40","doi-asserted-by":"crossref","unstructured":"Evans DS , et al. Proteomic Analysis of the Senescence-Associated Secretory Phenotype: GDF-15, IGFBP-2, and Cystatin-C Are Associated With Multiple Aging Traits. J Gerontol A Biol Sci Med Sci. 2024;79(3).","DOI":"10.1093\/gerona\/glad265"},{"issue":"1","key":"2026072217151648000_2026.05.28.728065v2.41","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s12890-016-0249-6","article-title":"Raised serum levels of IGFBP-1 and IGFBP-2 in idiopathic pulmonary fibrosis","volume":"16","year":"2016","journal-title":"BMC Pulm Med"},{"key":"2026072217151648000_2026.05.28.728065v2.42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0171344"},{"key":"2026072217151648000_2026.05.28.728065v2.43","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201306-1141WS"},{"key":"2026072217151648000_2026.05.28.728065v2.44","doi-asserted-by":"crossref","unstructured":"Bridges JP , et al. Progressive lung fibrosis: reprogramming a genetically vulnerable bronchoalveolar epithelium. J Clin Invest. 2025;135(1).","DOI":"10.1172\/JCI183836"},{"key":"2026072217151648000_2026.05.28.728065v2.45","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-019-0322-7"},{"key":"2026072217151648000_2026.05.28.728065v2.46","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-020-0542-8"},{"key":"2026072217151648000_2026.05.28.728065v2.47","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202004-1274OC"},{"key":"2026072217151648000_2026.05.28.728065v2.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.11.027"},{"key":"2026072217151648000_2026.05.28.728065v2.49","doi-asserted-by":"crossref","unstructured":"Lehmann M , et al. Senolytic drugs target alveolar epithelial cell function and attenuate experimental lung fibrosis ex vivo. Eur Respir J. 2017;50(2).","DOI":"10.1183\/13993003.02367-2016"},{"key":"2026072217151648000_2026.05.28.728065v2.50","doi-asserted-by":"crossref","unstructured":"Schafer MJ , et al. Cellular senescence mediates fibrotic pulmonary disease. Nat Commun. 2017;8:14532.","DOI":"10.1038\/ncomms14532"},{"key":"2026072217151648000_2026.05.28.728065v2.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2020.06.020"},{"key":"2026072217151648000_2026.05.28.728065v2.52","doi-asserted-by":"crossref","unstructured":"Katzen J , et al. An SFTPC BRICHOS mutant links epithelial ER stress and spontaneous lung fibrosis. JCI Insight. 2019;4(6).","DOI":"10.1172\/jci.insight.126125"},{"key":"2026072217151648000_2026.05.28.728065v2.53","doi-asserted-by":"publisher","DOI":"10.1172\/JCI99287"},{"key":"2026072217151648000_2026.05.28.728065v2.54","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez LR , et al. Impaired AMPK control of alveolar epithelial cell metabolism promotes pulmonary fibrosis. JCI Insight. 2025;10(15).","DOI":"10.1172\/jci.insight.182578"},{"key":"2026072217151648000_2026.05.28.728065v2.55","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.95"},{"key":"2026072217151648000_2026.05.28.728065v2.56","doi-asserted-by":"crossref","unstructured":"Marin TL , et al. AMPK promotes mitochondrial biogenesis and function by phosphorylating the epigenetic factors DNMT1, RBBP7, and HAT1. Sci Signal. 2017;10(464).","DOI":"10.1126\/scisignal.aaf7478"},{"key":"2026072217151648000_2026.05.28.728065v2.57","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0087-6"},{"key":"2026072217151648000_2026.05.28.728065v2.58","doi-asserted-by":"crossref","unstructured":"Baker JR , et al. Hallmarks of the ageing lung - 10 years later. Eur Respir J. 2026.","DOI":"10.1183\/13993003.01272-2025"},{"issue":"3","key":"2026072217151648000_2026.05.28.728065v2.59","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1152\/physrev.00024.2025","article-title":"Fueling the fire: metabolic dysfunction and senescence as drivers of lung aging and disease","volume":"106","year":"2026","journal-title":"Physiol Rev"},{"issue":"2","key":"2026072217151648000_2026.05.28.728065v2.60","doi-asserted-by":"crossref","first-page":"110662","DOI":"10.1016\/j.celrep.2022.110662","article-title":"Progenitor potential of lung epithelial organoid cells in a transplantation model","volume":"39","year":"2022","journal-title":"Cell Rep"},{"key":"2026072217151648000_2026.05.28.728065v2.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2021.11.014"},{"key":"2026072217151648000_2026.05.28.728065v2.62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0121246"},{"key":"2026072217151648000_2026.05.28.728065v2.63","doi-asserted-by":"crossref","unstructured":"Zhang K , et al. Acquisition of cellular properties during alveolar formation requires differential activity and distribution of mitochondria. Elife. 2022;11.","DOI":"10.7554\/eLife.68598"},{"key":"2026072217151648000_2026.05.28.728065v2.64","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax0860"},{"key":"2026072217151648000_2026.05.28.728065v2.65","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00524-z"},{"issue":"1","key":"2026072217151648000_2026.05.28.728065v2.66","first-page":"367","article-title":"Age-Associated Activation of the cGAS-STING Pathway and Impairment of DNA Damage Repair in Human Primary Alveolar Type II Cells","volume":"17","year":"2025","journal-title":"Aging Dis"},{"key":"2026072217151648000_2026.05.28.728065v2.67","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1705499114"},{"key":"2026072217151648000_2026.05.28.728065v2.68","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00062.2019"},{"key":"2026072217151648000_2026.05.28.728065v2.69","doi-asserted-by":"crossref","unstructured":"Radwanska A , et al. Increased expression and accumulation of GDF15 in IPF extracellular matrix contribute to fibrosis. JCI Insight. 2022;7(16).","DOI":"10.1172\/jci.insight.153058"},{"key":"2026072217151648000_2026.05.28.728065v2.70","doi-asserted-by":"crossref","unstructured":"Raffensperger K , et al. Endothelial GDF15 deficiency enhances barrier function and mitigates pulmonary fibrosis. JCI Insight. 2026.","DOI":"10.1172\/jci.insight.200198"},{"key":"2026072217151648000_2026.05.28.728065v2.71","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnad008"},{"key":"2026072217151648000_2026.05.28.728065v2.72","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-1154-2"},{"issue":"1","key":"2026072217151648000_2026.05.28.728065v2.73","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s40478-023-01557-2","article-title":"IGFBP2 promotes proliferation and cell migration through STAT3 signaling in Sonic hedgehog medulloblastoma","volume":"11","year":"2023","journal-title":"Acta Neuropathol Commun"},{"key":"2026072217151648000_2026.05.28.728065v2.74","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-0438"},{"key":"2026072217151648000_2026.05.28.728065v2.75","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2014.435"},{"issue":"3","key":"2026072217151648000_2026.05.28.728065v2.76","doi-asserted-by":"crossref","first-page":"106151","DOI":"10.1016\/j.isci.2023.106151","article-title":"IGFBP2 derived from PO-MSCs promote epithelial barrier destruction by activating FAK signaling in nasal polyps","volume":"26","year":"2023","journal-title":"iScience"},{"key":"2026072217151648000_2026.05.28.728065v2.77","doi-asserted-by":"crossref","unstructured":"Chin C , et al. Loss of IGFBP2 mediates alveolar type 2 cell senescence and promotes lung fibrosis. Cell Reports Medicine. 2023;4(3).","DOI":"10.1016\/j.xcrm.2023.100945"},{"key":"2026072217151648000_2026.05.28.728065v2.78","doi-asserted-by":"crossref","unstructured":"Sideris D , et al. Suppression of interferon signaling via small-molecule modulation of TFAM. Elife. 2026;14.","DOI":"10.7554\/eLife.108742"},{"key":"2026072217151648000_2026.05.28.728065v2.79","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00183214"},{"key":"2026072217151648000_2026.05.28.728065v2.80","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00084.2017"},{"key":"2026072217151648000_2026.05.28.728065v2.81","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2019-0276TR"},{"key":"2026072217151648000_2026.05.28.728065v2.82","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1117988108"},{"key":"2026072217151648000_2026.05.28.728065v2.83","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2020.109588"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.05.28.728065","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:15:29Z","timestamp":1784765729000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.05.28.728065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,30]]},"references-count":83,"URL":"https:\/\/doi.org\/10.64898\/2026.05.28.728065","relation":{},"subject":[],"published":{"date-parts":[[2026,5,30]]},"subtype":"preprint"}}