{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T03:52:08Z","timestamp":1789098728676,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T00:00:00Z","timestamp":1716768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874259"],"award-info":[{"award-number":["81874259"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173494"],"award-info":[{"award-number":["82173494"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Trichloroethylene (TCE) is a commonly used organic solvent in industry. Our previous studies have found that TCE can cause liver injury accompanied by macrophage polarization, but the specific mechanism is unclear. The epigenetic regulation of macrophage polarization is mainly focused on histone modification. Histone lysine demethylase 4A (KDM4A) is involved in the activation of macrophages. In this study, we used a mouse model we investigated the role of KDM4A in the livers of TCE\u2010drinking mice and found that the expression of KDM4A, M1\u2010type polarization indicators, and related inflammatory factors in the livers of TCE\u2010drinking mice. In the study, BALB\/c mice were randomly divided into four groups: 2.5\u2009mg\/mL TCE dose group and 5.0\u2009mg\/mL TCE dose group, the vehicle control group, and the blank control group. We found that TCE triggered M1 polarization of mouse macrophages, characterized by the expression of CD11c and robust production of inflammatory cytokines. Notably, exposure to TCE resulted in markedly increased expression of KDM4A in macrophages. Functionally, the increased expression of KDM4A significantly impaired the expression of H3K9me3 and H3K9me2 and increased the expression of H3K9me1. In addition, KDM4A potentially represents a novel epigenetic modulator, with its upregulation connected to \u03b2\u2010catenin activation, a signal critical for the pro\u2010inflammatory activation of macrophages. Furthermore, KDM4A inhibitor JIB\u201004 treatment resulted in a decrease in \u03b2\u2010catenin expression and prevented TCE\u2010induced M1 polarization and the expression of the pro\u2010inflammatory cytokines TNF\u2010\u03b1 and IL\u20101\u03b2. These results suggest that the association of KDM4A and Wnt\/\u03b2\u2010catenin cooperatively establishes the activation and polarization of macrophages and global changes in H3K9me3\/me2\/me1. Our findings identify KDM4A as an essential regulator of the polarization of macrophages and the expression of inflammatory cytokines, which might serve as a potential target for preventing and treating liver injury caused by TCE.<\/jats:p>","DOI":"10.1002\/cbin.12187","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T09:35:03Z","timestamp":1716802503000},"page":"1148-1159","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Histone demethylase KDM4A mediating macrophage polarization: A potential mechanism of trichloroethylene induced liver injury"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0064-604X","authenticated-orcid":false,"given":"Jiaxiang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Occupational Health and Environmental Health, School of Public Health Anhui Medical University Hefei Anhui China"},{"name":"Institute of Dermatology, Key Laboratory of Dermatology Ministry of Education Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Occupational Health and Environmental Health, School of Public Health Anhui Medical University Hefei Anhui China"},{"name":"Department Of Infectious Disease Prevention and Control Linan District Center for Disease Control and Prevention Hangzhou City Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baiwang","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Occupational Health and Environmental Health, School of Public Health Anhui Medical University Hefei Anhui China"},{"name":"Department Of Infectious Disease Prevention and Control Linan District Center for Disease Control and Prevention Hangzhou City Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibing","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Dermatology, Key Laboratory of Dermatology Ministry of Education Hefei Anhui China"},{"name":"Department of Dermatology First Affiliated Hospital of Anhui Medical University Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daojun","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Medical Technology Anhui Medical College Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulong","family":"Li","sequence":"additional","affiliation":[{"name":"The Center for Scientific Research Anhui Medical University Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Occupational Health and Environmental Health, School of Public Health Anhui Medical University Hefei Anhui China"},{"name":"Institute of Dermatology, Key Laboratory of Dermatology Ministry of Education Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qixing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Dermatology, Key Laboratory of Dermatology Ministry of Education Hefei Anhui China"},{"name":"Department of Dermatology First Affiliated Hospital of Anhui Medical University Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.32567"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2017.04.012"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/mop.0b013e32832925.cc"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-4300"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cotox.2017.11.013"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0000000000000109"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13183"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8091032"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.005457"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29106"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2020.109553"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.01433"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1039\/c9em00565j"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-20-0328"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx0255976"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12569"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/6591703"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2020.111453"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.01.030"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/1091581818757036"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-03-775569"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2019.05.156"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-022-03326-x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/08923973.2017.1364262"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2016.08.006"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10565-019-09479-3"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.12.025"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26607"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2020.109972"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.12.017"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgv057"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2019.05.203"},{"key":"e_1_2_11_34_1","first-page":"42","article-title":"Present situation of trichloroethylene production and consumption and market prospect","volume":"41","author":"Yao L.","year":"2013","journal-title":"Guangzhou Chemical Industry"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00538"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1177\/0748233717731213"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106897"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2019.01.015"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2018.03.024"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1080\/08923973.2020.1811306"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/1348-9585.12142"}],"container-title":["Cell Biology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbin.12187","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T04:27:11Z","timestamp":1721017631000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbin.12187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,27]]},"references-count":40,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1002\/cbin.12187"],"URL":"https:\/\/doi.org\/10.1002\/cbin.12187","archive":["Portico"],"relation":{},"ISSN":["1065-6995","1095-8355"],"issn-type":[{"value":"1065-6995","type":"print"},{"value":"1095-8355","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,27]]},"assertion":[{"value":"2024-01-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}