{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:34:36Z","timestamp":1791920076308,"version":"4.3.4"},"reference-count":51,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173881"],"award-info":[{"award-number":["82173881"]}],"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":["82003840"],"award-info":[{"award-number":["82003840"]}],"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":["8217130428"],"award-info":[{"award-number":["8217130428"]}],"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":["82025034"],"award-info":[{"award-number":["82025034"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013314","name":"Higher Education Discipline Innovation Project","doi-asserted-by":"publisher","award":["B16047"],"award-info":[{"award-number":["B16047"]}],"id":[{"id":"10.13039\/501100013314","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017688","name":"Guangdong Provincial Key Laboratory of Construction Foundation","doi-asserted-by":"publisher","award":["2020B1212060034"],"award-info":[{"award-number":["2020B1212060034"]}],"id":[{"id":"10.13039\/501100017688","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2019A1515010247"],"award-info":[{"award-number":["2019A1515010247"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Endotoxemia\u2010related acute liver injury has a poor prognosis and high mortality, and macrophage polarization plays a central role in the pathological process. Pregnane X receptor (PXR) serves as a nuclear receptor and xenosensor, safeguarding the liver from toxic stimuli. However, the effect and underlying mechanism of PXR activation on endotoxemic liver injury remain largely unknown. Here, the expression of PXR is reported in human and murine macrophages, and PXR activation modified immunotypes of macrophages. Moreover, PXR activation significantly attenuated endotoxemic liver injury and promoted macrophage M2 polarization. Macrophage depletion by GdCl<jats:sub>3<\/jats:sub> confirmed the essential of macrophages in the beneficial effects observed with PXR activation. The role of PXR in macrophages is further validated using AAV8\u2010<jats:italic>F4\/80<\/jats:italic>\u2010<jats:italic>Pxr<\/jats:italic> shRNA\u2010treated mice; the PXR\u2010mediated hepatoprotection is impaired, and M2 polarization enhancement is blunted. Additionally, treatment with PXR agonists inhibited lipopolysaccharide (LPS)\u2010induced M1 polarization and favored M2 polarization in BMDM, Raw264.7, and THP\u20101 cells. Further analyses revealed an interaction between PXR and p\u2010STAT6 in vivo and in vitro. Moreover, blocking <jats:italic>Pxr<\/jats:italic> or <jats:italic>Stat6<\/jats:italic> abolished the PXR\u2010induced polarization shift. Collectively, macrophage PXR activation attenuated endotoxin\u2010induced liver injury and regulated macrophage polarization through the STAT6 signaling pathway, which provided a potential therapeutic target for managing endotoxemic liver injury.<\/jats:p>","DOI":"10.1002\/advs.202308771","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T08:27:17Z","timestamp":1710318437000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Pregnane X Receptor Activation in Liver Macrophages Protects against Endotoxin\u2010Induced Liver Injury"],"prefix":"10.1002","volume":"11","author":[{"given":"Tingting","family":"Zhao","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Design and Evaluation School of Pharmaceutical Sciences Sun Yat\u2010Sen University  Guangzhou 510006 China"},{"name":"Institute of Clinical Pharmacology Sun Yat\u2010Sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoping","family":"Zhong","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Design and Evaluation School of Pharmaceutical Sciences Sun Yat\u2010Sen University  Guangzhou 510006 China"},{"name":"Institute of Clinical Pharmacology Sun Yat\u2010Sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010Sen Memorial Hospital Sun Yat\u2010Sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjie","family":"Cao","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Design and Evaluation School of Pharmaceutical Sciences Sun Yat\u2010Sen University  Guangzhou 510006 China"},{"name":"Institute of Clinical Pharmacology Sun Yat\u2010Sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaofei","family":"Song","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Design and Evaluation School of Pharmaceutical Sciences Sun Yat\u2010Sen University  Guangzhou 510006 China"},{"name":"Institute of Clinical Pharmacology Sun Yat\u2010Sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Design and Evaluation School of Pharmaceutical Sciences Sun Yat\u2010Sen University  Guangzhou 510006 China"},{"name":"Institute of Clinical Pharmacology Sun Yat\u2010Sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohui","family":"Wan","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Design and Evaluation School of Pharmaceutical Sciences Sun Yat\u2010Sen University  Guangzhou 510006 China"},{"name":"Institute of Clinical Pharmacology Sun Yat\u2010Sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Food and Drug Shenzhen Polytechnic University  Shenzhen 518055 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Design and Evaluation School of Pharmaceutical Sciences Sun Yat\u2010Sen University  Guangzhou 510006 China"},{"name":"Institute of Clinical Pharmacology Sun Yat\u2010Sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huichang","family":"Bi","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &amp; Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical Sciences Southern Medical University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4894-177X","authenticated-orcid":false,"given":"Yiming","family":"Jiang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Design and Evaluation School of Pharmaceutical Sciences Sun Yat\u2010Sen University  Guangzhou 510006 China"},{"name":"Institute of Clinical Pharmacology Sun Yat\u2010Sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,13]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-012418-012718"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.168"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02229-1"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2008.08.009"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.11"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2015.08.020"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.10.005"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45444"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.30956"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0463-9"},{"key":"e_1_2_9_9_3","doi-asserted-by":"publisher","DOI":"10.1126\/science.aai8132"},{"key":"e_1_2_9_9_4","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32609"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20215376"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2006.04.021"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902151"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2019.06.012"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2008.02721.x"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2011.06.058"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00791-1"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.01.024"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107676"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30131"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b08972"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.02.026"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26754"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells8050420"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-012-0562-3"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.45"},{"key":"e_1_2_9_20_3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032112"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80439-2"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-200107000-00002"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41368-022-00180-6"},{"key":"e_1_2_9_22_3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011297"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2019.112302"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-020-01364-0"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108132200"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2014.12.022"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2012.07.003"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2010.04.012"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01743360"},{"key":"e_1_2_9_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(98)00360-9"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1179\/joc.2004.16.4.357"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(18)30454-9"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.25633"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.08.020"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.04.037"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30990"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.3693"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00627-y"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2021.118214"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32105"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202308771","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T21:16:02Z","timestamp":1759958162000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202308771"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,13]]},"references-count":51,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1002\/advs.202308771"],"URL":"https:\/\/doi.org\/10.1002\/advs.202308771","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,13]]},"assertion":[{"value":"2023-11-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2308771"}}