{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:51:47Z","timestamp":1792173107822,"version":"4.4.0"},"reference-count":53,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Epidemiological evidence links environmental pollution to chronic kidney disease (CKD). However, the molecular mechanisms by which diesel\u2010derived pollutants trigger and sustain renal fibrosis are still unclear. In this study, we show that 1\u2010aminopyrene (1\u2010AP), a metabolite of diesel exhaust, leads to genomic instability and renal tubular epithelial cell (RTEC) senescence. Exposure of RTECs to sub\u2010cytotoxic concentrations of 1\u2010AP caused persistent DNA damage, as shown by comet assay and \u03b3\u2010H2AX foci. Sustained DNA damage activated the p21\u2010mediated cellular senescence, followed by induction of SASP factors (IL\u20106, IL\u20101\u03b2, CXCL1, MCP\u20101, and TGF\u2010\u03b21). Conditioned media from senescent RTECs promoted activation and extracellular matrix gene expression in renal fibroblasts, establishing epithelial\u2013mesenchymal crosstalk as a key driver of fibrogenic signaling. Although 1\u2010AP activated aryl hydrocarbon receptor (AhR) but AhR inhibition failed to suppress SASP expression and fibroblast activation. On epigenetic level, 1\u2010AP exposure on RTECs causes chromatin remodeling characterized by increased H3K9 acetylation and loss of H3K9me3 and H3K27me3, facilitating recruitment of the epigenetic reader BRD4 to SASP gene loci. Pharmacological inhibition of BRD4 suppressed SASP transcription, blocked paracrine activation of fibroblast and promotes apoptosis of RTECs. Hence, BRD4 may be a potential therapeutic target for treating pollution\u2010related CKD.<\/jats:p>","DOI":"10.1002\/jbt.71124","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:51:53Z","timestamp":1791377513000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Renal Tubular Epithelial Cells Senescence Induced by 1\u2010Aminopyrene Activates Fibroblast via BRD4 Driven Senescence\u2010Associated Secretory Phenotype Signaling"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5662-2621","authenticated-orcid":false,"given":"Atul","family":"Katarkar","sequence":"first","affiliation":[{"name":"Environmental Health and Toxicology CSIR\u2010National Environmental Engineering Research Institute Nagpur India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6869-5578","authenticated-orcid":false,"given":"Ankita","family":"Bagde","sequence":"additional","affiliation":[{"name":"Environmental Health and Toxicology CSIR\u2010National Environmental Engineering Research Institute Nagpur India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2717-4883","authenticated-orcid":false,"given":"Diwakar","family":"Maurya","sequence":"additional","affiliation":[{"name":"Environmental Health and Toxicology CSIR\u2010National Environmental Engineering Research Institute Nagpur India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavana","family":"Chahare","sequence":"additional","affiliation":[{"name":"Environmental Health and Toxicology CSIR\u2010National Environmental Engineering Research Institute Nagpur India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1805-6914","authenticated-orcid":false,"given":"Namita","family":"Mane","sequence":"additional","affiliation":[{"name":"Environmental Health and Toxicology CSIR\u2010National Environmental Engineering Research Institute Nagpur India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saravanadevi","family":"Sivanesan","sequence":"additional","affiliation":[{"name":"Environmental Health and Toxicology CSIR\u2010National Environmental Engineering Research Institute Nagpur India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1213-4984","authenticated-orcid":false,"given":"K.","family":"Krishnamurthi","sequence":"additional","affiliation":[{"name":"Environmental Health and Toxicology CSIR\u2010National Environmental Engineering Research Institute Nagpur India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00520"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP284289"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.105294"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0000000000000605"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1256375"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.569322"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2009.74"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1085605"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.17327"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.21037\/tau-24-214"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-16-0217"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1522163112"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114153"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32977-0"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13030678"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2018.11"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-51554-1"},{"key":"e_1_2_9_19_1","first-page":"183","article-title":"Fine Particulate Matter (PM2. 5) and Chronic Kidney Disease","volume":"254","author":"Zhang Y.","year":"2021","journal-title":"Reviews of Environmental Contamination and Toxicology"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/annweh\/wxx111"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43188-021-00096-z"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10661-021-09121-y"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15062"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1539\/joh.47.261"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11785-7"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1089\/aivt.2016.0026"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/i3090937"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2020.115798"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1797.2012.01572.x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2440"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-024-01968-1"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfaf190"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.02.031"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10600"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-121808-102144"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090517"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3218"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14532"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-022-00914-6"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15705"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.782199"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-019-2054-5"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2017.06.008"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05492-3"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05327"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00401-X"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.12.055"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.06.027"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.645593"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.112.081661"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.04.013"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12344"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.16031219"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2017030253"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.71124","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.71124","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.71124","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:23:10Z","timestamp":1792171390000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.71124"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":53,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/jbt.71124"],"URL":"https:\/\/doi.org\/10.1002\/jbt.71124","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-04-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71124"}}