{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:47:02Z","timestamp":1791978422430,"version":"4.4.0"},"reference-count":64,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T00:00:00Z","timestamp":1699833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004374","name":"Chongqing Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004374","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013314","name":"Higher Education Discipline Innovation Project","doi-asserted-by":"publisher","award":["D20028"],"award-info":[{"award-number":["D20028"]}],"id":[{"id":"10.13039\/501100013314","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":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although the dysregulation of bile acid (BA) composition has been associated with fibrosis progression, its precise roles in liver fibrosis is poorly understood. This study demonstrates that solute carrier family 27 member 5 (SLC27A5), an enzyme involved in BAs metabolism, is substantially downregulated in the liver tissues of patients with cirrhosis and fibrosis mouse models. The downregulation of SLC27A5 depends on RUNX family transcription factor 2 (RUNX2), which serves as a transcriptional repressor. The findings reveal that experimental SLC27A5 knockout (<jats:italic>Slc27a5<\/jats:italic><jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>) mice display spontaneous liver fibrosis after 24\u00a0months. The loss of SLC27A5 aggravates liver fibrosis induced by carbon tetrachloride (CCI<jats:sub>4<\/jats:sub>) and thioacetamide (TAA). Mechanistically, SLC27A5 deficiency results in the accumulation of unconjugated BA, particularly cholic acid (CA), in the liver. This accumulation leads to the activation of hepatic stellate cells (HSCs) by upregulated expression of early growth response protein 3 (EGR3). The re\u2010expression of hepatic SLC27A5 by an adeno\u2010associated virus or the reduction of CA levels in the liver using A4250, an apical sodium\u2010dependent bile acid transporter (ASBT) inhibitor, ameliorates liver fibrosis in Slc27a5<jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice. In conclusion, SLC27A5 deficiency in mice drives hepatic fibrosis through CA\u2010induced activation of HSCs, highlighting its significant implications for liver fibrosis treatment.<\/jats:p>","DOI":"10.1002\/advs.202304408","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T23:15:14Z","timestamp":1699917314000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Loss of SLC27A5 Activates Hepatic Stellate Cells and Promotes Liver Fibrosis via Unconjugated Cholic Acid"],"prefix":"10.1002","volume":"11","author":[{"given":"Kang","family":"Wu","sequence":"first","affiliation":[{"name":"Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education) Institute for Viral Hepatitis Department of Infectious Diseases The Second Affiliated Hospital Chongqing Medical University  Chongqing 400010 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education) Institute for Viral Hepatitis Department of Infectious Diseases The Second Affiliated Hospital Chongqing Medical University  Chongqing 400010 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education) Institute for Viral Hepatitis Department of Infectious Diseases The Second Affiliated Hospital Chongqing Medical University  Chongqing 400010 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiale","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Life Sciences Chongqing Medical University  Chongqing 400016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education) Institute for Viral Hepatitis Department of Infectious Diseases The Second Affiliated Hospital Chongqing Medical University  Chongqing 400010 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijun","family":"Liang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education) Institute for Viral Hepatitis Department of Infectious Diseases The Second Affiliated Hospital Chongqing Medical University  Chongqing 400010 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengli","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education) Institute for Viral Hepatitis Department of Infectious Diseases The Second Affiliated Hospital Chongqing Medical University  Chongqing 400010 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education) Institute for Viral Hepatitis Department of Infectious Diseases The Second Affiliated Hospital Chongqing Medical University  Chongqing 400010 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Nie","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education) Institute for Viral Hepatitis Department of Infectious Diseases The Second Affiliated Hospital Chongqing Medical University  Chongqing 400010 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education) Institute for Viral Hepatitis Department of Infectious Diseases The Second Affiliated Hospital Chongqing Medical University  Chongqing 400010 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ailong","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education) Institute for Viral Hepatitis Department of Infectious Diseases The Second Affiliated Hospital Chongqing Medical University  Chongqing 400010 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Life Sciences Chongqing Medical University  Chongqing 400016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5830-8786","authenticated-orcid":false,"given":"Ni","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education) Institute for Viral Hepatitis Department of Infectious Diseases The Second Affiliated Hospital Chongqing Medical University  Chongqing 400010 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,13]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2019.09.006"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32285"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.38"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.104720"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-021-00566-7"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.16602"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15035"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.5b00217"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.0c00852"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm-20-5110"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29076"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI132305"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32437"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.02.006"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M200260-JLR200"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.02.012"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11745-011-3596-3"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9416-3"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.02.004"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-019-01633-2"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1113"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.44774"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-019-0266-7"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-020-0467-3"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.06.016"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(22)00158-3"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-020-01595-w"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14453"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-019-08731-2"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.2217\/epi-2022-0362"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106248"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-019-0399-1"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6642939"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aohep.2022.100681"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30407"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-020-0471-4"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24087001"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12494"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306341"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700482R"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3233\/CBM-200472"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311804200"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12347"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12050792"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12876-018-0842-7"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2022.0327"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103290"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27240"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11030536"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107539"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01594-y"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(22)00093-0"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.01.007"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3160765"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2009.12.006"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2020.109800"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104274"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24967"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2022.115139"},{"key":"e_1_2_9_60_1","first-page":"13","volume":"7","author":"Zhang W.","year":"2012","journal-title":"PLoS One"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2015.017"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27452-9"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-021-02058-z"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1072"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202304408","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T14:38:54Z","timestamp":1759761534000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202304408"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,13]]},"references-count":64,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/advs.202304408"],"URL":"https:\/\/doi.org\/10.1002\/advs.202304408","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,13]]},"assertion":[{"value":"2023-07-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2304408"}}