{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:19:48Z","timestamp":1788434388101,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"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":["Hepatology Research"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Liver fibrosis is a progressive pathological condition characterized by excessive extracellular matrix (ECM) deposition, primarily driven by hepatic stellate cell (HSC) activation. Although Forkhead box S1 (FOXS1) has been implicated in fibrotic and neoplastic processes, its functional role in hepatic fibrosis and its regulatory mechanisms remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      FOXS1 expression was analyzed in human fibrotic liver tissues, CCl\n                      <jats:sub>4<\/jats:sub>\n                      \u2010induced, and methionine\u2010choline\u2010deficient (MCD) diet\u2010induced nonalcoholic steatohepatitis (NASH) mouse models and activated HSCs. CCl\n                      <jats:sub>4<\/jats:sub>\n                      \u2010induced and MCD mouse models of liver fibrosis and TGF\u2010\u03b21\u2010stimulated LX\u20102 and HSC\u2010T6 cells and H\u2010HSCs and M\u2010HSCs were used to investigate FOXS1 function in vivo and in vitro. TGF\u2010\u03b21\u2010induced fibrosis models were used to explore the FOXS1\u2010TGF\u2010\u03b21\/Smad axis in HSC activation. Furthermore, functional assays, luciferase reporter, RNA pulldown, MeRIP, and RIP assays were conducted to elucidate the regulatory relationships among FOXS1, miR\u2010212\u20105p, and m6A demethylase FTO.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>FOXS1 expression was elevated in fibrotic human and mouse liver tissues and positively correlated with fibrosis severity. FOXS1 knockdown in mice ameliorated fibrosis, reduced ECM protein expression, and improved liver function. In HSCs, FOXS1 enhanced TGF\u2010\u03b21\/Smad2\/3 signaling in a positive feedback loop, promoting HSC activation, migration, and resistance to apoptosis. Mechanistically, miR\u2010212\u20105p directly targeted FOXS1 and suppressed fibrogenesis, but its maturation was inhibited by FTO\u2010mediated m6A demethylation of pri\u2010miR\u2010212. Additionally, FTO knockdown promoted miR\u2010212\u20105p processing, downregulated FOXS1, and disrupted the TGF\u2010\u03b21\/Smad loop, thereby exerting antifibrotic effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>FOXS1 acts as a novel driver of hepatic fibrosis that promotes HSC activation through TGF\u2010\u03b21\/Smad\u2010dependent feedback loop involving FTO\u2010mediated m6A modification and miR\u2010212\u20105p. Targeting the FTO\/miR\u2010212\u20105p\/FOXS1 axis offers a promising therapeutic strategy for liver fibrosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hepr.70208","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T12:37:21Z","timestamp":1780663041000},"page":"1402-1418","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FOXS1 Promotes Liver Fibrosis Through TGF\u2010\u03b21\/Smad Signaling: Targeting a Novel miR\u2010212\u20105p\/FTO Axis"],"prefix":"10.1111","volume":"56","author":[{"given":"Maoqun","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery Affiliated Hospital of Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Xinghua City People's Hospital Affiliated to Yangzhou University  Taizhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Xinghua City People's Hospital Affiliated to Yangzhou University  Taizhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benshun","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery Affiliated Hospital of Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingyi","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Affiliated Hospital of Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoyang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Taizhou People's Hospital  Taizhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Institute of Translational Medicine Affiliated Hospital of Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5955-6500","authenticated-orcid":false,"given":"Donglin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery Affiliated Hospital of Jiangnan University  Wuxi Jiangsu China"},{"name":"Department of Hepatobiliary and Pancreatic Surgery Third Affiliated Hospital of Soochow University  Changzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery Affiliated Hospital of Jiangnan University  Wuxi Jiangsu China"},{"name":"Department of General Surgery Yancheng Clinical Medical College of Jiangsu University, The First People's Hospital of Yancheng  Yancheng Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9040875"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575\u2010020\u201000372\u20107"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2018.09.002"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.03.017"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i23.7312"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.38"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201042058\u2010z"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154626"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2023.12.012"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2022.2052530"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010024\u201001764\u2010w"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010021\u201000781\u20103"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010024\u201003114\u20108"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/hc9.0000000000000342"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111318"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010022\u201003525\u20101"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201041717\u2010w"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.12392"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1866"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.105691"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010019\u20101994\u20102"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.24757"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00322"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00379.2006"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12265\u2010021\u201010156\u20102"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.3724\/abbs.2024098"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.2147\/ijgm.s354195"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.115893"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2004.11.009"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.05.004"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1369\/0022155415627681"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.48"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.116733"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1039\/d1fo02657g"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf070"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095\u2010014\u20101497\u2010x"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs20150427"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389557523666230328125031"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm\u201021\u20105005"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22189799"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14281"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2003733117"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12033\u2010023\u201000921\u2010w"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2022.11484"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23073800"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203404"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094537"}],"container-title":["Hepatology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hepr.70208","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hepr.70208","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hepr.70208","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:51:48Z","timestamp":1788432708000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hepr.70208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,5]]},"references-count":47,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/hepr.70208"],"URL":"https:\/\/doi.org\/10.1111\/hepr.70208","archive":["Portico"],"relation":{},"ISSN":["1386-6346","1872-034X"],"issn-type":[{"value":"1386-6346","type":"print"},{"value":"1872-034X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,5]]},"assertion":[{"value":"2025-06-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}