{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T19:01:38Z","timestamp":1785265298987,"version":"3.55.0"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005851","name":"Shahid Beheshti University of Medical Sciences","doi-asserted-by":"publisher","award":["936"],"award-info":[{"award-number":["936"]}],"id":[{"id":"10.13039\/501100005851","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":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The activation of hepatic stellate cells is the primary function of facilitating liver fibrosis. Interfering with the coordinators of different signaling pathways in activated hepatic stellate cells (aHSCs) could be a potential approach in ameliorating liver fibrosis. Regarding the illustrated anti\u2010fibrotic effect of imatinib in liver fibrosis, we investigated the imatinib\u2032s potential role in inhibiting HSC activation through miR\u2010124 and its interference with the STAT3\/hepatic leukemia factor (HLF)\/IL\u20106 circuit. The anti\u2010fibrotic effect of imatinib was investigated in the LX\u20102 cell line and carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)\u2010induced Sprague\u2010Dawley rat. The expression of IL\u20106, STAT3, HLF, miR\u2010124, and \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) were quantified by quantitative real\u2010time PCR (qRT\u2010PCR) and the protein level of \u03b1\u2010SMA and STAT3 was measured by western blot analysis both in vitro and in vivo. The LX\u20102 cells were subjected to immunocytochemistry (ICC) for \u03b1\u2010SMA expression. After administering imatinib in the liver fibrosis model, histopathological examinations were done, and hepatic function serum markers were checked. Imatinib administration alleviated mentioned liver fibrosis markers. The expression of miR\u2010124 was downregulated, while IL\u20106\/HLF\/STAT3 circuit agents were upregulated in vitro and in vivo. Notably, imatinib intervention decreased the expression of IL\u20106, STAT3, and HLF. Elevated expression of miR\u2010124 suppressed the expression of STAT3 and further inhibited HSCs activation. Our results demonstrated that imatinib not only ameliorated hepatic fibrosis through tyrosine kinase inhibitor (TKI) activity but also interfered with the miR\u2010124 and STAT3\/HLF\/IL\u20106 pathway. Considering the important role of miR\u2010124 in regulating liver fibrosis and HSCs activation, imatinib may exert its anti\u2010fibrotic activity through miR\u2010124.<\/jats:p>","DOI":"10.1002\/cbin.11992","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T09:22:48Z","timestamp":1674120168000},"page":"969-980","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Imatinib suppresses activation of hepatic stellate cells by targeting STAT3\/IL\u20106 pathway through miR\u2010124"],"prefix":"10.1002","volume":"47","author":[{"given":"Helia","family":"Alavifard","sequence":"first","affiliation":[{"name":"Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases Shahid Beheshti University of Medical Sciences Tehran Iran"},{"name":"Research Center for Liver Disease, Keck School of Medicine University of Southern California Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sogol","family":"Mazhari","sequence":"additional","affiliation":[{"name":"Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases Shahid Beheshti University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Meyfour","sequence":"additional","affiliation":[{"name":"Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases Shahid Beheshti University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samaneh","family":"Tokhanbigli","sequence":"additional","affiliation":[{"name":"Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases Shahid Beheshti University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeid","family":"Ghavami","sequence":"additional","affiliation":[{"name":"Research Institute in Oncology and Hematology, Cancer Care Manitoba University of Manitoba Winnipeg Manitoba Canada"},{"name":"Autophagy Research Center Shiraz University of Medical Sciences Shiraz Iran"},{"name":"Faculty of Medicine Katowice School of Technology Katowice Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Reza","family":"Zali","sequence":"additional","affiliation":[{"name":"Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases Shahid Beheshti University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid Asadzadeh","family":"Aghdaei","sequence":"additional","affiliation":[{"name":"Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases Shahid Beheshti University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behzad","family":"Hatami","sequence":"additional","affiliation":[{"name":"Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases Shahid Beheshti University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2102-9729","authenticated-orcid":false,"given":"Kaveh","family":"Baghaei","sequence":"additional","affiliation":[{"name":"Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases Shahid Beheshti University of Medical Sciences Tehran Iran"},{"name":"Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases Shahid Beheshti University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2011.09.008"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1711449114"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25879"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/158547"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020461"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2017.09.035"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13665"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2020.112162"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00372.2017"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2007.07.006"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2008.11.025"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1755-1536-3-21"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1998.275.2.G269"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1609324"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-60615-0"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19071889"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i29.6652"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-017-0161-7"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0176173"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9010024"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.4132\/jptm.2016.08.08"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-00372-7"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2012.00069"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-016-0300-3"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173263"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016081"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2025242118"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9040875"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3978\/j.issn.2304-3881.2015.01.05"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.4084\/mjhid.2014.007"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.02.004"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19010261"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2011.02.004"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.12286"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055509"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.38"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-019-0324-8"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2621"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00513"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2020.1761203"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-313392"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.10.033"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.426"},{"issue":"4","key":"e_1_2_10_45_1","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s00011-016-1020-4","article-title":"miR\u2010200a controls hepatic stellate cell activation and fibrosis via SIRT1\/Notch1 signal pathway","volume":"66","author":"Yang J.\u2010J.","year":"2017","journal-title":"Inflammation Research: Official Journal of the European Histamine Research Society"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-021-02358-x"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.7641"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00420.2004"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c170053"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i48.10512"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-019-5462-8"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgw011"}],"container-title":["Cell Biology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbin.11992","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbin.11992","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbin.11992","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T22:27:40Z","timestamp":1692570460000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbin.11992"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,19]]},"references-count":51,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["10.1002\/cbin.11992"],"URL":"https:\/\/doi.org\/10.1002\/cbin.11992","archive":["Portico"],"relation":{},"ISSN":["1065-6995","1095-8355"],"issn-type":[{"value":"1065-6995","type":"print"},{"value":"1095-8355","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,19]]},"assertion":[{"value":"2022-07-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}