{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:15:31Z","timestamp":1785406531165,"version":"3.56.0"},"posted":{"date-parts":[[2026,3,11]]},"group-title":"Pathology","reference-count":69,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["CA219150"],"award-info":[{"award-number":["CA219150"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["HL157533"],"award-info":[{"award-number":["HL157533"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["HL24127301"],"award-info":[{"award-number":["HL24127301"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Rationale<\/jats:title>\n                  <jats:p>Progressive fibrosing interstitial lung disease features \u201cadvancing fronts\u201d where new matrix is deposited, but the signals sustaining these propagating niches remain incompletely defined.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To determine the spatial and temporal compartments in which HIF-1\u03b1 operates during fibrotic progression and to test whether myeloid HIF-1\u03b1 is a tractable driver of lesion propagation.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We integrated human IPF datasets, clinical severity profiling, sarcoidosis peripheral blood immune phenotyping, multiplex immunofluorescence and spatial mapping in human lung tissue, single-cell transcriptomic analyses, and temporally staged bleomycin lung injury with genetic and lung-directed therapeutic perturbations.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Measurements and Main Results<\/jats:title>\n                  <jats:p>In the Lung Genome Research Consortium cohort, HIF1A expression was increased in IPF lungs and correlated with higher GAP scores. In sarcoidosis, circulating monocytes from patients with progressive disease exhibited increased HIF-1\u03b1 compared with those with resolving disease. In IPF lungs, nuclear HIF-1\u03b1 localized predominantly to CD68\u207a macrophages and PDGFR\u03b1\u207a fibroblasts concentrated within collagen-rich, \u03b1SMA\u207a advancing fronts, and single-cell analyses demonstrated enrichment of HIF-1\u03b1-linked transcriptional programs consistent with macrophage-fibroblast crosstalk (including pro-fibrotic growth factors, chemokines, and matrix-regulatory pathways). In bleomycin-induced fibrosis, HIF-1\u03b1 activity emerged first in macrophages and subsequently in fibroblasts within pimonidazole-marked hypoxic rims bordering nascent \u03b1SMA\u207a foci. Myeloid-specific Hif1a deletion reduced front-associated macrophage persistence, attenuated fibroblast activation, and decreased collagen deposition. Two lung-directed strategies, inhaled liposomal echinomycin and inhaled shHif1a lipid nanoparticles, phenocopied these effects, demonstrating therapeutic tractability.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These findings define a hypoxic front-zone niche in which myeloid HIF-1\u03b1 sustains macrophage persistence and promotes fibroblast activation and matrix remodeling. By linking spatial compartmentalization to causal genetics and lung-directed intervention, our work identifies myeloid HIF-1\u03b1 as a mechanism-anchored, locally targetable driver of fibrotic lesion propagation.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.09.710578","type":"posted-content","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:25:14Z","timestamp":1773285914000},"source":"Crossref","is-referenced-by-count":0,"title":["Myeloid HIF-1\u03b1 Sustains Hypoxic Fibrotic Fronts and Drives Pulmonary Fibrosis"],"prefix":"10.64898","author":[{"given":"Yuanyi","family":"Wei","sequence":"first","affiliation":[{"name":"Division of Immunotherapy, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Bailey","sequence":"additional","affiliation":[{"name":"Division of Immunotherapy, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Beijing Children\u2019s Hospital, Capital Medical University, National Cancer for Children\u2019s Health, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Herazo-Maya","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of South Florida, Morsani College of Medicine, Tampa, FL 33612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodoros","family":"Karampitsakos","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of South Florida, Morsani College of Medicine, Tampa, FL 33612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Pescrille","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felisa","family":"Diaz-Mendez","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andriy","family":"Samokhin","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Immunotherapy, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonder","family":"Drake","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4749-3768","authenticated-orcid":false,"given":"Yin","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Immunotherapy, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026031315402147000_2026.03.09.710578v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30866-8"},{"key":"2026031315402147000_2026.03.09.710578v1.2","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1159\/000509556","article-title":"Progressive fibrosing interstitial lung diseases: Prevalence and characterization in two italian referral centers","volume":"99","year":"2020","journal-title":"Respiration; international review of thoracic diseases"},{"key":"2026031315402147000_2026.03.09.710578v1.3","doi-asserted-by":"crossref","unstructured":"Chianese M , Screm G , Salton F , Confalonieri P , Trotta L , Barbieri M , Ruggero L , Mari M , Reccardini N , Geri P , Hughes M , Lerda S , Confalonieri M , Mondini L , Ruaro B . Pirfenidone and nintedanib in pulmonary fibrosis: Lights and shadows. Pharmaceuticals 2024;17.","DOI":"10.3390\/ph17060709"},{"key":"2026031315402147000_2026.03.09.710578v1.4","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2023.2213436"},{"key":"2026031315402147000_2026.03.09.710578v1.5","doi-asserted-by":"crossref","unstructured":"Herrera JA , Dingle L , Montero MA , Venkateswaran RV , Blaikley JF , Lawless C , Schwartz MA . The uip\/ipf fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix. JCI insight 2022;7.","DOI":"10.1172\/jci.insight.156115"},{"key":"2026031315402147000_2026.03.09.710578v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-024-01819-2"},{"key":"2026031315402147000_2026.03.09.710578v1.7","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/s41577-025-01186-x","article-title":"The spatial and temporal activation of macrophages during fibrosis","volume":"25","year":"2025","journal-title":"Nature reviews Immunology"},{"key":"2026031315402147000_2026.03.09.710578v1.8","doi-asserted-by":"publisher","DOI":"10.1172\/JCI84426"},{"key":"2026031315402147000_2026.03.09.710578v1.9","doi-asserted-by":"crossref","unstructured":"Brereton CJ , Yao L , Davies ER , Zhou Y , Vukmirovic M , Bell JA , Wang S , Ridley RA , Dean LSN , Andriotis OG , Conforti F , Brewitz L , Mohammed S , Wallis T , Tavassoli A , Ewing RM , Alzetani A , Marshall BG , Fletcher SV , Thurner PJ , Fabre A , Kaminski N , Richeldi L , Bhaskar A , Schofield CJ , Loxham M , Davies DE , Wang Y , Jones MG . Pseudohypoxic hif pathway activation dysregulates collagen structure-function in human lung fibrosis. eLife 2022;11.","DOI":"10.7554\/eLife.69348"},{"key":"2026031315402147000_2026.03.09.710578v1.10","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1007\/s00109-018-1710-1","article-title":"Hypoxia-inducible factor-1alpha regulation of myeloid cells","volume":"96","year":"2018","journal-title":"Journal of molecular medicine"},{"key":"2026031315402147000_2026.03.09.710578v1.11","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abo5254"},{"key":"2026031315402147000_2026.03.09.710578v1.12","doi-asserted-by":"crossref","unstructured":"Mia MM , Ghani S , Cibi DM , Bogireddi H , Nilanthi U , Selvan A , Wong WSF , Singh MK . Yap\/taz are crucial regulators of macrophage-mediated pulmonary inflammation and fibrosis after bleomycin-induced injury. The European respiratory journal 2025;65.","DOI":"10.1183\/13993003.01544-2023"},{"key":"2026031315402147000_2026.03.09.710578v1.13","doi-asserted-by":"crossref","unstructured":"Tanner L , Single AB , Bhongir RKV , Heusel M , Mohanty T , Karlsson CAQ , Pan L , Clausson CM , Bergwik J , Wang K , Andersson CK , Oommen RM , Erjefalt JS , Malmstrom J , Wallner O , Boldogh I , Helleday T , Kalderen C , Egesten A . Small-molecule-mediated ogg1 inhibition attenuates pulmonary inflammation and lung fibrosis in a murine lung fibrosis model. Nature communications 2023;14:643.","DOI":"10.1038\/s41467-023-36314-5"},{"key":"2026031315402147000_2026.03.09.710578v1.14","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1038\/s41587-024-02437-3","article-title":"Lung and liver editing by lipid nanoparticle delivery of a stable crispr-cas9 ribonucleoprotein","volume":"43","year":"2025","journal-title":"Nature biotechnology"},{"key":"2026031315402147000_2026.03.09.710578v1.15","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-2808"},{"key":"2026031315402147000_2026.03.09.710578v1.16","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.121.000668"},{"key":"2026031315402147000_2026.03.09.710578v1.17","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.189340"},{"key":"2026031315402147000_2026.03.09.710578v1.18","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M602178200"},{"key":"2026031315402147000_2026.03.09.710578v1.19","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200705-683OC"},{"key":"2026031315402147000_2026.03.09.710578v1.20","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2014.0150"},{"key":"2026031315402147000_2026.03.09.710578v1.21","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-019-0258-7"},{"key":"2026031315402147000_2026.03.09.710578v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/nri2448"},{"key":"2026031315402147000_2026.03.09.710578v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2807"},{"key":"2026031315402147000_2026.03.09.710578v1.24","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/neup.12111","article-title":"Angiogenesis and expression of pdgf-c, vegf, cd105 and hif-1alpha in human glioblastoma","volume":"34","year":"2014","journal-title":"Neuropathology : official journal of the Japanese Society of Neuropathology"},{"key":"2026031315402147000_2026.03.09.710578v1.25","doi-asserted-by":"crossref","unstructured":"Saddouk FZ , Kuzemczak A , Saito J , Greif DM . Endothelial hifalpha\/pdgf-b to smooth muscle beclin1 signaling sustains pathological muscularization in pulmonary hypertension. JCI insight 2024;9.","DOI":"10.1172\/jci.insight.162449"},{"key":"2026031315402147000_2026.03.09.710578v1.26","doi-asserted-by":"crossref","unstructured":"Bordag N , Biasin V , Schnoegl D , Valzano F , Jandl K , Nagy BM , Sharma N , Wygrecka M , Kwapiszewska G , Marsh LM . Machine learning analysis of the bleomycin mouse model reveals the compartmental and temporal inflammatory pulmonary fingerprint. iScience 2020;23:101819.","DOI":"10.1016\/j.isci.2020.101819"},{"key":"2026031315402147000_2026.03.09.710578v1.27","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20162152"},{"key":"2026031315402147000_2026.03.09.710578v1.28","doi-asserted-by":"crossref","unstructured":"Morse C , Tabib T , Sembrat J , Buschur KL , Bittar HT , Valenzi E , Jiang Y , Kass DJ , Gibson K , Chen W , Mora A , Benos PV , Rojas M , Lafyatis R . Proliferating spp1\/mertk-expressing macrophages in idiopathic pulmonary fibrosis. The European respiratory journal 2019;54.","DOI":"10.1183\/13993003.02441-2018"},{"key":"2026031315402147000_2026.03.09.710578v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-01975-x"},{"key":"2026031315402147000_2026.03.09.710578v1.30","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202202-0399ST"},{"key":"2026031315402147000_2026.03.09.710578v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.01.010"},{"key":"2026031315402147000_2026.03.09.710578v1.32","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1186\/s12885-024-13104-w","article-title":"Efficacy and toxicity of lurbinectedin in subsequent systemic therapy of extensive-stage small cell lung cancer: A meta-analysis","volume":"24","year":"2024","journal-title":"BMC cancer"},{"key":"2026031315402147000_2026.03.09.710578v1.33","doi-asserted-by":"crossref","unstructured":"Bailey CM , Liu Y , Peng G , Zhang H , He M , Sun D , Zheng P , Liu Y , Wang Y . Liposomal formulation of hif-1alpha inhibitor echinomycin eliminates established metastases of triple-negative breast cancer. Nanomedicine : nanotechnology, biology, and medicine 2020;29:102278.","DOI":"10.1016\/j.nano.2020.102278"},{"key":"2026031315402147000_2026.03.09.710578v1.34","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1038\/s41388-020-1201-z","article-title":"Therapeutic targeting of tp53-mutated acute myeloid leukemia by inhibiting hif-1alpha with echinomycin","volume":"39","year":"2020","journal-title":"Oncogene"},{"key":"2026031315402147000_2026.03.09.710578v1.35","doi-asserted-by":"crossref","first-page":"4809","DOI":"10.1038\/s41388-021-01907-1","article-title":"Targeting the hif-1alpha-igfbp2 axis therapeutically reduces igf1-akt signaling and blocks the growth and metastasis of relapsed anaplastic wilms tumor","volume":"40","year":"2021","journal-title":"Oncogene"},{"key":"2026031315402147000_2026.03.09.710578v1.36","doi-asserted-by":"crossref","unstructured":"Peng G , Wang Y , Ge P , Bailey C , Zhang P , Zhang D , Meng Z , Qi C , Chen Q , Chen J , Niu J , Zheng P , Liu Y , Liu Y . The hif1alpha-pdgfd-pdgfralpha axis controls glioblastoma growth at normoxia\/mild-hypoxia and confers sensitivity to targeted therapy by echinomycin. Journal of experimental & clinical cancer research : CR 2021;40:278.","DOI":"10.1186\/s13046-021-02082-7"},{"key":"2026031315402147000_2026.03.09.710578v1.37","doi-asserted-by":"crossref","unstructured":"Zhang L , Wang Y , Wu G , Xiong W , Gu W , Wang CY . Macrophages: Friend or foe in idiopathic pulmonary fibrosis? Respiratory research 2018;19:170.","DOI":"10.1186\/s12931-018-0864-2"},{"key":"2026031315402147000_2026.03.09.710578v1.38","doi-asserted-by":"crossref","unstructured":"Aquino-Galvez A , Gonzalez-Avila G , Jimenez-Sanchez LL , Maldonado-Martinez HA , Cisneros J , Toscano-Marquez F , Castillejos-Lopez M , Torres-Espindola LM , Velazquez-Cruz R , Rodriguez VHO , Flores-Soto E , Solis-Chagoyan H , Cabello C , Zuniga J , Romero Y . Dysregulated expression of hypoxia-inducible factors augments myofibroblasts differentiation in idiopathic pulmonary fibrosis. Respiratory research 2019;20:130.","DOI":"10.1186\/s12931-019-1100-4"},{"key":"2026031315402147000_2026.03.09.710578v1.39","doi-asserted-by":"crossref","unstructured":"Delbrel E , Soumare A , Naguez A , Label R , Bernard O , Bruhat A , Fafournoux P , Tremblais G , Marchant D , Gille T , Bernaudin JF , Callard P , Kambouchner M , Martinod E , Valeyre D , Uzunhan Y , Planes C , Boncoeur E . Hif-1alpha triggers er stress and chop-mediated apoptosis in alveolar epithelial cells, a key event in pulmonary fibrosis. Scientific reports 2018;8:17939.","DOI":"10.1038\/s41598-018-36063-2"},{"key":"2026031315402147000_2026.03.09.710578v1.40","doi-asserted-by":"crossref","unstructured":"Epstein Shochet G , Bardenstein-Wald B , McElroy M , Kukuy A , Surber M , Edelstein E , Pertzov B , Kramer MR , Shitrit D . Hypoxia inducible factor 1a supports a pro-fibrotic phenotype loop in idiopathic pulmonary fibrosis. International journal of molecular sciences 2021;22.","DOI":"10.3390\/ijms22073331"},{"key":"2026031315402147000_2026.03.09.710578v1.41","doi-asserted-by":"crossref","unstructured":"Romero Y , Balderas-Martinez YI , Vargas-Morales MA , Castillejos-Lopez M , Vazquez-Perez JA , Calyeca J , Torres-Espindola LM , Patino N , Camarena A , Carlos-Reyes A , Flores-Soto E , Leon-Reyes G , Sierra-Vargas MP , Herrera I , Luis-Garcia ER , Ruiz V , Velazquez-Cruz R , Aquino-Galvez A . Effect of hypoxia in the transcriptomic profile of lung fibroblasts from idiopathic pulmonary fibrosis. Cells 2022;11.","DOI":"10.3390\/cells11193014"},{"key":"2026031315402147000_2026.03.09.710578v1.42","doi-asserted-by":"crossref","unstructured":"Yang L , Gilbertsen A , Xia H , Benyumov A , Smith K , Herrera J , Racila E , Bitterman PB , Henke CA . Hypoxia enhances ipf mesenchymal progenitor cell fibrogenicity via the lactate\/gpr81\/hif1alpha pathway. JCI insight 2023;8.","DOI":"10.1172\/jci.insight.163820"},{"key":"2026031315402147000_2026.03.09.710578v1.43","doi-asserted-by":"crossref","first-page":"e15759","DOI":"10.14814\/phy2.15759","article-title":"Persistent hypoxia promotes myofibroblast differentiation via gpr-81 and differential regulation of ldh isoenzymes in normal and idiopathic pulmonary fibrosis fibroblasts","volume":"11","year":"2023","journal-title":"Physiological reports"},{"key":"2026031315402147000_2026.03.09.710578v1.44","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba1983"},{"key":"2026031315402147000_2026.03.09.710578v1.45","doi-asserted-by":"publisher","DOI":"10.1164\/RCCM.201712-2410OC\/SUPPL_FILE\/DISCLOSURES.PDF"},{"key":"2026031315402147000_2026.03.09.710578v1.46","doi-asserted-by":"crossref","unstructured":"Froom Z , Callaghan NI , Davenport Huyer L . Cellular crosstalk in fibrosis: Insights into macrophage and fibroblast dynamics. The Journal of biological chemistry 2025;301:110203.","DOI":"10.1016\/j.jbc.2025.110203"},{"key":"2026031315402147000_2026.03.09.710578v1.47","doi-asserted-by":"crossref","unstructured":"Kolb P , Upagupta C , Vierhout M , Ayaub E , Bellaye PS , Gauldie J , Shimbori C , Inman M , Ask K , Kolb MRJ . The importance of interventional timing in the bleomycin model of pulmonary fibrosis. The European respiratory journal 2020;55.","DOI":"10.1183\/13993003.01105-2019"},{"key":"2026031315402147000_2026.03.09.710578v1.48","doi-asserted-by":"crossref","unstructured":"Cui H , Jiang D , Banerjee S , Xie N , Kulkarni T , Liu RM , Duncan SR , Liu G . Monocyte-derived alveolar macrophage apolipoprotein e participates in pulmonary fibrosis resolution. JCI insight 2020;5.","DOI":"10.1172\/jci.insight.134539"},{"key":"2026031315402147000_2026.03.09.710578v1.49","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1038\/s41467-025-57024-0","article-title":"Trem2 promotes lung fibrosis via controlling alveolar macrophage survival and pro-fibrotic activity","volume":"16","year":"2025","journal-title":"Nature communications"},{"key":"2026031315402147000_2026.03.09.710578v1.50","doi-asserted-by":"crossref","unstructured":"Lu W , Teoh A , Waters M , Haug G , Shakeel I , Hassan I , Shahzad AM , Callerfelt AL , Piccari L , Sohal SS . Pathology of idiopathic pulmonary fibrosis with particular focus on vascular endothelium and epithelial injury and their therapeutic potential. Pharmacology & therapeutics 2025;265:108757.","DOI":"10.1016\/j.pharmthera.2024.108757"},{"key":"2026031315402147000_2026.03.09.710578v1.51","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.biocel.2007.08.011","article-title":"The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis?","volume":"40","year":"2008","journal-title":"The international journal of biochemistry & cell biology"},{"key":"2026031315402147000_2026.03.09.710578v1.52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0059348"},{"key":"2026031315402147000_2026.03.09.710578v1.53","doi-asserted-by":"crossref","unstructured":"Miura Y , Lam M , Bourke JE , Kanazawa S . Bimodal fibrosis in a novel mouse model of bleomycin-induced usual interstitial pneumonia. Life science alliance 2022;5.","DOI":"10.1101\/2021.03.18.435059"},{"key":"2026031315402147000_2026.03.09.710578v1.54","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20092121"},{"key":"2026031315402147000_2026.03.09.710578v1.55","doi-asserted-by":"crossref","first-page":"L109","DOI":"10.1152\/ajplung.00176.2018","article-title":"Flow cytometric analysis of the leukocyte landscape during bleomycin-induced lung injury and fibrosis in the rat","volume":"317","year":"2019","journal-title":"American journal of physiology Lung cellular and molecular physiology"},{"key":"2026031315402147000_2026.03.09.710578v1.56","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.10.5735"},{"key":"2026031315402147000_2026.03.09.710578v1.57","first-page":"63","article-title":"Lymphocyte aggregates persist and accumulate in the lungs of patients with idiopathic pulmonary fibrosis","volume":"6","year":"2013","journal-title":"Journal of inflammation research"},{"key":"2026031315402147000_2026.03.09.710578v1.58","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201309-1592OC"},{"key":"2026031315402147000_2026.03.09.710578v1.59","doi-asserted-by":"crossref","unstructured":"Cocconcelli E , Balestro E , Turato G , Fiorentu G , Bazzan E , Biondini D , Tine M , Bernardinello N , Pezzuto F , Baraldo S , Calabrese F , Rea F , Sanduzzi Zamparelli A , Spagnolo P , Cosio MG , Saetta M . Tertiary lymphoid structures and b-cell infiltration are ipf features with functional consequences. Frontiers in immunology 2024;15:1437767.","DOI":"10.3389\/fimmu.2024.1437767"},{"key":"2026031315402147000_2026.03.09.710578v1.60","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.3389\/fimmu.2020.02190","article-title":"Identification of a novel hif-1alpha-alpha(m)beta(2) integrin-net axis in fibrotic interstitial lung disease","volume":"11","year":"2020","journal-title":"Frontiers in immunology"},{"key":"2026031315402147000_2026.03.09.710578v1.61","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.3389\/fimmu.2017.01618","article-title":"Promoter specificity and efficacy in conditional and inducible transgenic targeting of lung macrophages","volume":"8","year":"2017","journal-title":"Frontiers in immunology"},{"key":"2026031315402147000_2026.03.09.710578v1.62","first-page":"3130","article-title":"Mouse models and tools for the in vivo study of neutrophils","volume":"10","year":"2019","journal-title":"Frontiers in immunology"},{"key":"2026031315402147000_2026.03.09.710578v1.63","doi-asserted-by":"crossref","unstructured":"Wan Q , Zhang X , Zhou D , Xie R , Cai Y , Zhang K , Sun X . Inhaled nano-based therapeutics for pulmonary fibrosis: Recent advances and future prospects. Journal of nanobiotechnology 2023;21:215.","DOI":"10.1186\/s12951-023-01971-7"},{"key":"2026031315402147000_2026.03.09.710578v1.64","doi-asserted-by":"crossref","unstructured":"Massaro M , Wu S , Baudo G , Liu H , Collum S , Lee H , Stigliano C , Segura-Ibarra V , Karmouty-Quintana H , Blanco E . Lipid nanoparticle-mediated mrna delivery in lung fibrosis. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 2023;183:106370.","DOI":"10.1016\/j.ejps.2023.106370"},{"key":"2026031315402147000_2026.03.09.710578v1.65","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.xfss.2022.01.005","article-title":"Antitumor effect of the selective hypoxia-inducible factor-1 inhibitors echinomycin and px-478 on uterine fibroids","volume":"3","year":"2022","journal-title":"F&S science"},{"key":"2026031315402147000_2026.03.09.710578v1.66","doi-asserted-by":"crossref","unstructured":"Zeng Y , Wei Y , Chen C , Shen J , Qian J , Ma X , Su M , Zhang T , Yu B , Zhu C , Wang S . Ss-hpt nanocarrier delivery of hif-1alpha-shrna reduces pathological lactylation and alleviates inflammation in a sustained hypoxia mouse model. International journal of biological macromolecules 2025;325:146903.","DOI":"10.1016\/j.ijbiomac.2025.146903"},{"key":"2026031315402147000_2026.03.09.710578v1.67","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.omtm.2021.01.003","article-title":"Gene therapy strategies for idiopathic pulmonary fibrosis: Recent advances, current challenges, and future directions","volume":"20","year":"2021","journal-title":"Molecular therapy Methods & clinical development"},{"key":"2026031315402147000_2026.03.09.710578v1.68","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.41.4.467"},{"key":"2026031315402147000_2026.03.09.710578v1.69","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0193057"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.03.09.710578","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T22:40:34Z","timestamp":1773441634000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.03.09.710578"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,11]]},"references-count":69,"URL":"https:\/\/doi.org\/10.64898\/2026.03.09.710578","relation":{},"subject":[],"published":{"date-parts":[[2026,3,11]]},"subtype":"preprint"}}