{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:59:18Z","timestamp":1790290758821,"version":"4.1.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"<jats:p>\n                    PM2.5 is a major air pollutant associated with the onset and exacerbation of various diseases. However, due to the lack of suitable experimental models, the damage caused by PM2.5 to the organism and its relationship with diseases remain poorly understood. This study aims to establish a toxicity exposure model for PM2.5 using human alveolar organoids (hALOs) and investigate the differences in alveolar damage caused by water-extractable fraction and DMSO-extractable fraction of PM2.5. The results revealed that PM2.5 induced morphological damage in hALOs in a dose- and time-dependent manner, with the DMSO-extractable fraction eliciting more severe damage than the water-extractable fraction. PM2.5-induced increases in ROS levels and cell death were associated with the observed morphological damage. During the damage process, we also observed a sustained decline in the number of AT2 cells within the organoids, accompanied by a slight increase in the number of AT1 cells, suggesting that AT2-to-AT1 transdifferentiation may be occurring. This study helps advance the application of\n                    <jats:italic>in vitro<\/jats:italic>\n                    3D organoid models in toxicological research and facilitate a deeper integration of PM2.5 toxicology and pathology.\n                  <\/jats:p>","DOI":"10.3389\/ftox.2026.1943932","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:10:11Z","timestamp":1790287811000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential toxicity of water- and DMSO-extractable PM2.5 fractions in human alveolar organoids"],"prefix":"10.3389","volume":"8","author":[{"given":"Shasha","family":"Yu","sequence":"first","affiliation":[{"name":"School of Public Health, Wannan Medical University","place":["Wuhu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangyao","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Public Health, Wannan Medical University","place":["Wuhu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajie","family":"Pan","sequence":"additional","affiliation":[{"name":"School of Public Health, Wannan Medical University","place":["Wuhu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyang","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Public Health, Wannan Medical University","place":["Wuhu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyang","family":"Dai","sequence":"additional","affiliation":[{"name":"School of Public Health, Wannan Medical University","place":["Wuhu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaopeng","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Public Health, Wannan Medical University","place":["Wuhu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Public Health, Wannan Medical University","place":["Wuhu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1007\/s00441-016-2554-z","article-title":"The biology of the ABCA3 lipid transporter in lung health and disease","volume":"367","author":"Beers","year":"2017","journal-title":"Cell Tissue Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1261483","DOI":"10.3389\/fimmu.2023.1261483","article-title":"Lung inflammation and interstitial fibrosis by targeted alveolar epithelial type I cell death","volume":"14","author":"Carignon","year":"2023","journal-title":"Front. Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"108920","DOI":"10.1016\/j.pharmthera.2025.108920","article-title":"Air pollution and diseases: signaling, G protein-coupled and toll like receptors","volume":"275","author":"Cattani-Cavalieri","year":"2025","journal-title":"Pharmacol. Ther."},{"key":"B4","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/978-1-0716-3854-5_2","article-title":"Using 3-Dimensional cultures to propagate genetically modified lung organoids","volume":"2805","author":"Chen","year":"2024","journal-title":"Methods Mol. Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"123686","DOI":"10.1016\/j.envpol.2024.123686","article-title":"PM(2.5) induces a senescent state in mouse AT2 cells","volume":"347","author":"Cheng","year":"2024","journal-title":"Environ. Pollut."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e4657","DOI":"10.21769\/BioProtoc.4657","article-title":"Establishing bipotential human lung organoid culture system and differentiation to generate mature alveolar and airway organoids","volume":"13","author":"Chiu","year":"2023","journal-title":"Bio Protoc."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1016\/j.cell.2016.05.082","article-title":"Modeling development and disease with organoids","volume":"165","year":"2016","journal-title":"Cell"},{"key":"B8","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1164\/arrd.1980.122.1.123","article-title":"Structural and biochemical changes in rat lungs occurring during exposures to lethal and adaptive doses of oxygen","volume":"122","author":"Crapo","year":"1980","journal-title":"Am. Rev. Respir. Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"327","DOI":"10.2217\/rme.11.18","article-title":"Self-renewal and scalability of human embryonic stem cells for human therapy","volume":"6","author":"Fu","year":"2011","journal-title":"Regen. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"9951","DOI":"10.2147\/JIR.S514437","article-title":"PM2.5 induces cell-specific transcriptomic alterations in the lungs of juvenile mice","volume":"18","author":"Gui","year":"2025","journal-title":"J. Inflamm. Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"124913","DOI":"10.1016\/j.envpol.2024.124913","article-title":"PM2.5 induces developmental neurotoxicity in cortical organoids","volume":"361","author":"Han","year":"2024","journal-title":"Environ. Pollut."},{"key":"B12","doi-asserted-by":"publisher","first-page":"bio039453","DOI":"10.1242\/bio.039453","article-title":"Soft substrate maintains proliferative and adipogenic differentiation potential of human mesenchymal stem cells on long-term expansion by delaying senescence","volume":"8","author":"Kureel","year":"2019","journal-title":"Biol. Open"},{"key":"B13","doi-asserted-by":"publisher","first-page":"132227","DOI":"10.1016\/j.jhazmat.2023.132227","article-title":"Short-term PM(2.5) exposure induces transient lung injury and repair","volume":"459","author":"Li","year":"2023","journal-title":"J. Hazard Mater."},{"key":"B14","doi-asserted-by":"publisher","first-page":"108883","DOI":"10.1016\/j.envint.2024.108883","article-title":"Particulate matter induces depression-like behavior through systemic inflammation and brain-derived neurotrophic factors","volume":"194","author":"Li","year":"2024","journal-title":"Environ. International"},{"key":"B15","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s00431-025-06214-5","article-title":"Chemical constituents of PM(2.5) and their association with childhood asthma and lung function: a systematic review and meta-analysis","volume":"184","author":"Li","year":"2025","journal-title":"Eur. J. Pediatr."},{"key":"B16","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1038\/s41596-018-0104-8","article-title":"Generation of lung organoids from human pluripotent stem cells in vitro","volume":"14","author":"Miller","year":"2019","journal-title":"Nat. Protoc."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1126\/science.aam6603","article-title":"Single-cell wnt signaling niches maintain stemness of alveolar type 2 cells","volume":"359","author":"Nabhan","year":"2018","journal-title":"Science"},{"key":"B18","doi-asserted-by":"publisher","first-page":"22799036221148989","DOI":"10.1177\/22799036221148989","article-title":"PM(2.5) exposure and lung function impairment among fiber-cement industry workers","volume":"12","author":"Nasri","year":"2023","journal-title":"J. Public Health Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1093\/etojnl\/vgaf293","article-title":"Impact of extraction methods on ambient PM2.5 components and cytotoxicity","volume":"45","author":"She","year":"2026","journal-title":"Environ. Toxicol. Chem."},{"key":"B20","doi-asserted-by":"publisher","first-page":"240280","DOI":"10.1183\/16000617.0280-2024","article-title":"Air pollution and alveolar health","volume":"34","author":"Sofia","year":"2025","journal-title":"Eur. Respir. Rev."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e66417","DOI":"10.7554\/eLife.66417","article-title":"Adult stem cell-derived complete lung organoid models emulate lung disease in COVID-19","volume":"10","author":"Tindle","year":"2021","journal-title":"Elife"},{"key":"B22","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s00018-022-04640-4","article-title":"DNA barcoding and gene expression recording reveal the presence of cancer cells with unique properties during tumor progression","volume":"80","author":"Umeki","year":"2022","journal-title":"Cell Mol. Life Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"493","DOI":"10.2147\/copd.s402122","article-title":"The effects and pathogenesis of PM2.5 and its components on chronic obstructive pulmonary disease","volume":"18","author":"Wang","year":"2023","journal-title":"Int. J. Chron. Obstruct Pulmon Dis."},{"key":"B24","doi-asserted-by":"publisher","first-page":"121764","DOI":"10.1016\/j.envpol.2023.121764","article-title":"The developmental toxicity of PM2.5 on the early stages of fetal lung with human lung bud tip progenitor organoids","volume":"330","author":"Wang","year":"2023","journal-title":"Environ. Pollut."},{"key":"B25","doi-asserted-by":"publisher","first-page":"109525","DOI":"10.1016\/j.envint.2025.109525","article-title":"Air pollutants and lung regeneration: impact on the fate of lung stem cells","volume":"199","author":"Wu","year":"2025","journal-title":"Environ. Int."},{"key":"B26","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.mrgentox.2018.12.005","article-title":"Ambient fine particulate matter (PM(2.5)) induces oxidative stress and pro-inflammatory response via up-regulating the expression of CYP1A1\/1B1 in human bronchial epithelial cells in vitro","volume":"839","author":"Yuan","year":"2019","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen"},{"key":"B27","doi-asserted-by":"publisher","first-page":"607341","DOI":"10.3389\/fcell.2021.607341","article-title":"The impact of particulate matter (PM2.5) on human retinal development in hESC-Derived retinal organoids","volume":"9","author":"Zeng","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"B28","first-page":"339","article-title":"A study on the oxidative stress induced by ambient fine particulate matter (PM2.5) and water-soluble fraction on HBE cells","author":"Zhang","year":"2016","journal-title":"Prev. Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"3081","DOI":"10.1021\/acs.est.0c05814","article-title":"Chronic exposure to PM(2.5) nitrate, sulfate, and ammonium causes respiratory system impairments in mice","volume":"55","author":"Zhang","year":"2021","journal-title":"Environ. Sci. Technol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"100380","DOI":"10.1016\/j.impact.2022.100380","article-title":"Property-activity relationship between physicochemical properties of PM(2.5) and their activation of NLRP3 inflammasome","volume":"25","author":"Zheng","year":"2022","journal-title":"NanoImpact"},{"key":"B31","doi-asserted-by":"publisher","first-page":"20691","DOI":"10.18632\/oncotarget.7842","article-title":"Repeated PM2.5 exposure inhibits BEAS-2B cell P53 expression through ROS-Akt-DNMT3B pathway-mediated promoter hypermethylation","volume":"7","author":"Zhou","year":"2016","journal-title":"Oncotarget"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.3390\/pharmaceutics13081280","article-title":"Drug screening, oral bioavailability and regulatory aspects: a need for human organoids","volume":"13","author":"Zietek","year":"2021","journal-title":"Pharmaceutics"},{"key":"B33","doi-asserted-by":"publisher","first-page":"559","DOI":"10.3390\/bioengineering9100559","article-title":"Keratin promotes differentiation of keratinocytes seeded on collagen\/keratin hydrogels","volume":"9","author":"Zuniga","year":"2022","journal-title":"Bioeng. (Basel)"}],"container-title":["Frontiers in Toxicology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/ftox.2026.1943932\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:10:12Z","timestamp":1790287812000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/ftox.2026.1943932\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,25]]},"references-count":33,"alternative-id":["10.3389\/ftox.2026.1943932"],"URL":"https:\/\/doi.org\/10.3389\/ftox.2026.1943932","relation":{},"ISSN":["2673-3080"],"issn-type":[{"value":"2673-3080","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,25]]},"article-number":"1943932"}}