关键词： Dickkopf1 Hepatic fibrosis Wnt/β-catenin pathway enhancer of zeste homologue 2 histone methylation

Mesh ： Animals Carbon Tetrachloride Cell Line Cell Proliferation / drug effects genetics Cells, Cultured Enhancer of Zeste Homolog 2 Protein / genetics metabolism Gene Expression Regulation Hepatic Stellate Cells / drug effects metabolism Intercellular Signaling Peptides and Proteins / genetics metabolism Liver Cirrhosis / chemically induced genetics metabolism RNA Interference Rats, Sprague-Dawley Transforming Growth Factor beta1 / pharmacology Wnt Signaling Pathway / drug effects genetics

来  源：   DOI：10.1111/jcmm.13153   PDF(Sci-hub)

Abstract：
EZH2, a histone H3 lysine-27-specific methyltransferase, is involved in diverse physiological and pathological processes including cell proliferation and differentiation. However, the role of EZH2 in liver fibrosis is largely unknown. In this study, it was identified that EZH2 promoted Wnt pathway-stimulated fibroblasts in vitro and in vivo by repressing Dkk-1, which is a Wnt pathway antagonist. The expression of EZH2 was increased in CCl4 -induced rat liver and primary HSCs as well as TGF-β1-treated HSC-T6, whereas the expression of Dkk1 was reduced. Silencing of EZH2 prevented TGF-β1-induced proliferation of HSC-T6 cells and the expression of α-SMA. In addition, knockdown of Dkk1 promoted TGF-β1-induced activation of HSCs. Moreover, silencing of EZH2 could restore the repression of Dkk-1 through trimethylation of H3K27me3 in TGF-β1-treated HSC-T6 cells. Interestingly, inhibition of EZH2 had almost no effect on the activation of HSC when Dkk1 was silenced. Collectively, EZH2-mediated repression of Dkk1 promotes the activation of Wnt/β-catenin pathway, which is an essential event for HSC activation.
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