{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:11:25Z","timestamp":1790399485764,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T00:00:00Z","timestamp":1592438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004699","name":"Chung Shan Medical University Hospital","doi-asserted-by":"publisher","award":["CSH-2018-C-013"],"award-info":[{"award-number":["CSH-2018-C-013"]}],"id":[{"id":"10.13039\/501100004699","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Oral submucosal fibrosis (OSF) is a premalignant disorder of the oral cavity, and areca nut chewing is known to be a major etiological factor that could induce epithelial to mesenchymal transition (EMT) and activate buccal mucosal fibroblasts (BMFs). However, this detailed mechanism is not fully understood. In this study, we showed that the upregulation of Snail in OSF samples and fibrotic BMFs (fBMFs) may result from constant irritation by arecoline, a major alkaloid of the areca nut. The elevation of Snail triggered myofibroblast transdifferentiation and was crucial to the persistent activation of fBMFs. Meanwhile, Snail increased the expression of numerous fibrosis factors (e.g., \u03b1-SMA and collagen I) as well as IL-6. Results from bioinformatics software and a luciferase-based reporter assay revealed that IL-6 was a direct target of Snail. Moreover, IL-6 in BMFs was found to further increase the expression of Snail and mediate Snail-induced myofibroblast activation. These findings suggested that there was a positive loop between Snail and IL-6 to regulate the areca nut-associated myofibroblast transdifferentiation, which implied that the blockage of Snail may serve as a favorable therapeutic strategy for OSF treatment.<\/jats:p>","DOI":"10.3390\/cancers12061611","type":"journal-article","created":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T11:00:56Z","timestamp":1592478056000},"page":"1611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Positive Feedback Loop of SNAIL-IL-6 Mediates Myofibroblastic Differentiation Activity in Precancerous Oral Submucous Fibrosis"],"prefix":"10.3390","volume":"12","author":[{"given":"Chih-Yu","family":"Peng","sequence":"first","affiliation":[{"name":"School of Dentistry, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Dentistry, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Wen","family":"Liao","sequence":"additional","affiliation":[{"name":"School of Dentistry, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Dentistry, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Yi","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Dentistry, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Dentistry, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chieh-Mei","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Dentistry, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Ling","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Chia","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Dentistry, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Dentistry, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"},{"name":"Institute of Oral Sciences, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1111\/j.1600-0714.2007.00582.x","article-title":"Nomenclature and classification of potentially malignant disorders of the oral mucosa","volume":"36","author":"Warnakulasuriya","year":"2007","journal-title":"J. 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