Resveratrol suppresses myofibroblast activity of human buccal mucosal fibroblasts through the epigenetic inhibition of ZEB1 expression.

doi:10.18632/oncotarget.7763

中山醫學大學機構典藏 CSMUIR > 口腔醫學院 > 牙醫學系暨碩士班 > 期刊論文 > Item 310902500/15685

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题名:	Resveratrol suppresses myofibroblast activity of human buccal mucosal fibroblasts through the epigenetic inhibition of ZEB1 expression.
作者:	YC, Chang;CW, Lin;CC, Yu;BY, Wang;YH, Huang;YC, Hsieh;YL, Kuo;WW, Chang
贡献者:	中山醫學大學
关键词:	EZH2;H3K27me3;Pathology Section;ZEB1;oral submucous fibrosis;resveratrol
日期:	2016-02-26
上传时间:	2016-08-09T07:38:49Z (UTC)
ISSN:	1949-2553
摘要:	Oral submucous fibrosis (OSF) is a precancerous condition of the oral mucosa without specific therapeutic drugs. We previously demonstrated that the zinc finger E-box binding homeobox 1 (ZEB1) plays a pathogenic role in the induction of the myofibroblast activity of buccal mucosal fibroblasts (BMFs) and contributes to the pathogenesis of OSF. Resveratrol is a natural polyphenolic flavonoid with anti-fibrosis activity in various tissues and has the capability to inhibit ZEB1 in oral cancer cells. We examined the effect of resveratrol on the myofibroblast activity of human primary fibrotic BMFs (fBMFs) derived from OSF tissues. With the collagen contraction assay, resveratrol displayed anti-myofibroblast activity in three fBMF lines. Resveratrol also inhibited the expression of fibrogenic genes at the mRNA and protein levels in a dose- and time-dependent manner. The downregulation of ZEB1 in fBMFs by resveratrol was mediated by epigenetic mechanisms, such as the upregulated expression of miR-200c and the enhancer of zeste homolog 2 (EZH2), as well as the trimethylated lysine 27 of histone H3 (H3K27me3). Resveratrol also increased the binding of H3K27me3 to the ZEB1 promoter. The knockdown of EZH2 in fBMFs caused the upregulation of ZEB1 and suppressed the inhibitory effect of resveratrol. Furthermore, the reversed expression pattern between EZH2 and ZEB1 was observed in 6/8 OSF tissues with twofold upregulation of ZEB1 expression compared with the adjacent normal mucosa. In conclusion, our data suggest that resveratrol epigenetically inhibits ZEB1 expression to suppress the myofibroblast activity of fBMFs and may serve as a dietary supplement for OSF patients.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/15685 http://dx.doi.org/10.18632/oncotarget.7763
關聯:	Oncotarget. 2016 Mar 15;7(11):12137-49.
显示于类别:	[牙醫學系暨碩士班] 期刊論文

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