Arecoline‐induced myofibroblast transdifferentiation from human buccal mucosal fibroblasts is mediated by ZEB1

doi:10.1111/JCMM.12219

中山醫學大學機構典藏 CSMUIR > 醫學科技學院 > 生物醫學科學學系暨碩士班 > 期刊論文 > Item 310902500/20401

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/20401

Title:	Arecoline‐induced myofibroblast transdifferentiation from human buccal mucosal fibroblasts is mediated by ZEB1
Authors:	Chang, Yu‐Chao Tsai, Chung‐Hung Lai, You‐Liang Yu, Cheng‐Chia Chi, Wan‐Yu Li, Jung Jung Chang, Wen‐Wei
Contributors:	生物醫學科學學系
Keywords:	arecoline;myofibroblasts;buccal mucosal fibroblasts;ZEB1;oral submucous fibrosis;α‐SMA
Date:	2014-01
Issue Date:	2019-10-24T03:17:23Z (UTC)
Publisher:	Journal of Cellular and Molecular Medicine
ISSN:	1582-1838
Abstract:	Oral submucous fibrosis (OSF) is considered as a pre‐cancerous 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 OSF. Our previous studies have demonstrated that arecoline could induce epithelial–mesenchymal transition (EMT)‐related factors in primary human buccal mucosal fibroblasts (BMFs). Therefore, we investigated the expression of zinc finger E‐box binding homeobox 1 (ZEB1), which is a well‐known transcriptional factor in EMT, in OSF tissues and its role in arecoline‐induced myofibroblast transdifferentiation from BMFs. The expression of ZEB1, as well as the myofibroblast marker α‐smooth muscle actin (α‐SMA), was significantly increased in OSF tissues, respectively. With immunofluorescence analysis, arecoline induced the formation of α‐SMA‐positive stress fibres in BMFs expressing nuclear ZEB1. Arecoline also induced collagen contraction of BMFs in vitro. By chromatin immunoprecipitation, the binding of ZEB1 to the α‐SMA promoter in BMFs was increased by arecoline. The promoter activity of α‐SMA in BMFs was also induced by arecoline, while knockdown of ZEB1 abolished arecoline‐induced α‐SMA promoter activity and collagen contraction of BMFs. Long‐term exposure of BMFs to arecoline induced the expression of fibrogenic genes and ZEB1. Silencing of ZEB1 in fibrotic BMFs from an OSF patient also suppressed the expression of α‐SMA and myofibroblast activity. Inhibition of insulin‐like growth factor receptor‐1 could suppress arecoline‐induced ZEB1 activation in BMFs. Our data suggest that ZEB1 may participate in the pathogenesis of areca quid–associated OSF by activating the α‐SMA promoter and inducing myofibroblast transdifferentiation from BMFs.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/20401
Relation:	Journal of Cellular and Molecular Medicine, Vol. 18, Issue 4, 698-708
Appears in Collections:	[生物醫學科學學系暨碩士班] 期刊論文

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