{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T22:56:07Z","timestamp":1786575367269,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T00:00:00Z","timestamp":1389139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Oral submucous fibrosis (<jats:styled-content style=\"fixed-case\">OSF<\/jats:styled-content>) is considered as a pre\u2010cancerous condition of the oral mucosa and is highly associated with habitual areca quid chewing. Arecoline is the major alkaloid in areca quid and is thought to be involved in the pathogenesis of <jats:styled-content style=\"fixed-case\">OSF<\/jats:styled-content>. Our previous studies have demonstrated that arecoline could induce epithelial\u2013mesenchymal transition (<jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content>)\u2010related factors in primary human buccal mucosal fibroblasts (<jats:styled-content style=\"fixed-case\">BMF<\/jats:styled-content>s). Therefore, we investigated the expression of zinc finger E\u2010box binding homeobox 1 (<jats:styled-content style=\"fixed-case\">ZEB<\/jats:styled-content>1), which is a well\u2010known transcriptional factor in <jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content>, in <jats:styled-content style=\"fixed-case\">OSF<\/jats:styled-content> tissues and its role in arecoline\u2010induced myofibroblast transdifferentiation from <jats:styled-content style=\"fixed-case\">BMF<\/jats:styled-content>s. The expression of <jats:styled-content style=\"fixed-case\">ZEB<\/jats:styled-content>1, as well as the myofibroblast marker \u03b1\u2010smooth muscle actin (\u03b1\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>), was significantly increased in <jats:styled-content style=\"fixed-case\">OSF<\/jats:styled-content> tissues, respectively. With immunofluorescence analysis, arecoline induced the formation of \u03b1\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>\u2010positive stress fibres in <jats:styled-content style=\"fixed-case\">BMF<\/jats:styled-content>s expressing nuclear <jats:styled-content style=\"fixed-case\">ZEB<\/jats:styled-content>1. Arecoline also induced collagen contraction of <jats:styled-content style=\"fixed-case\">BMF<\/jats:styled-content>s <jats:italic>in vitro<\/jats:italic>. By chromatin immunoprecipitation, the binding of <jats:styled-content style=\"fixed-case\">ZEB<\/jats:styled-content>1 to the \u03b1\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> promoter in <jats:styled-content style=\"fixed-case\">BMF<\/jats:styled-content>s was increased by arecoline. The promoter activity of \u03b1\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">BMF<\/jats:styled-content>s was also induced by arecoline, while knockdown of <jats:styled-content style=\"fixed-case\">ZEB<\/jats:styled-content>1 abolished arecoline\u2010induced \u03b1\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> promoter activity and collagen contraction of <jats:styled-content style=\"fixed-case\">BMF<\/jats:styled-content>s. Long\u2010term exposure of <jats:styled-content style=\"fixed-case\">BMF<\/jats:styled-content>s to arecoline induced the expression of fibrogenic genes and <jats:styled-content style=\"fixed-case\">ZEB<\/jats:styled-content>1. Silencing of <jats:styled-content style=\"fixed-case\">ZEB<\/jats:styled-content>1 in fibrotic <jats:styled-content style=\"fixed-case\">BMF<\/jats:styled-content>s from an <jats:styled-content style=\"fixed-case\">OSF<\/jats:styled-content> patient also suppressed the expression of \u03b1\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> and myofibroblast activity. Inhibition of insulin\u2010like growth factor receptor\u20101 could suppress arecoline\u2010induced <jats:styled-content style=\"fixed-case\">ZEB<\/jats:styled-content>1 activation in <jats:styled-content style=\"fixed-case\">BMF<\/jats:styled-content>s. Our data suggest that <jats:styled-content style=\"fixed-case\">ZEB<\/jats:styled-content>1 may participate in the pathogenesis of areca quid\u2013associated <jats:styled-content style=\"fixed-case\">OSF<\/jats:styled-content> by activating the \u03b1\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> promoter and inducing myofibroblast transdifferentiation from <jats:styled-content style=\"fixed-case\">BMF<\/jats:styled-content>s.<\/jats:p>","DOI":"10.1111\/jcmm.12219","type":"journal-article","created":{"date-parts":[[2014,1,9]],"date-time":"2014-01-09T02:05:13Z","timestamp":1389233113000},"page":"698-708","source":"Crossref","is-referenced-by-count":130,"title":["Arecoline\u2010induced myofibroblast transdifferentiation from human buccal mucosal fibroblasts is mediated by <scp>ZEB<\/scp>1"],"prefix":"10.1111","volume":"18","author":[{"given":"Yu\u2010Chao","family":"Chang","sequence":"first","affiliation":[{"name":"School of Dentistry Chung Shan Medical University Taichung Taiwan"},{"name":"Department of Dentistry Chung Shan Medical University Hospital Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung\u2010Hung","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Pathology Chung Shan Medical University Hospital Taichung Taiwan"},{"name":"Institute of Medicine Chung Shan Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You\u2010Liang","family":"Lai","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences Chung Shan Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng\u2010Chia","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Dentistry Chung Shan Medical University Taichung Taiwan"},{"name":"Department of Dentistry Chung Shan Medical University Hospital Taichung Taiwan"},{"name":"Institute of Oral Science Chung Shan Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan\u2010Yu","family":"Chi","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences Chung Shan Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Jung","family":"Li","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences Chung Shan Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Wei","family":"Chang","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences Chung Shan Medical University Taichung Taiwan"},{"name":"Department of Medical Research Chung Shan Medical University Hospital Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,1,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2005.08.005"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0714.2001.300404.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2005.00339.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2786"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2009.09.020"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.070112"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1368-8375(02)00123-9"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2005.05.006"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2006.06.007"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1368-8375(01)00083-5"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-012-0935-3"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a124267"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2011050485"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.03.026"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2007.00633.x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/549041"},{"key":"e_1_2_7_18_1","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/S0021-9258(18)48383-4","article-title":"Elements of the smooth muscle alpha\u2010actin promoter required in cis for transcriptional activation in smooth muscle. 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