山西医科大学学报2023,Vol.54Issue(12):1577-1584,8.DOI:10.13753/j.issn.1007-6611.2023.12.005
姜黄素通过EZH2/PPARγ途径抑制肝星状细胞活化
Curcumin inhibits activation of hepatic stellate cells through EZH2/PPARγ pathway
摘要
Abstract
Objective To investigate the molecular mechanism of curcumin inhibiting the activation of hepatic stellate cells(HSCs).Methods Rat hepatic stellate cells HSC-T6 were divided into control group,transforming growth factor-β1(TGF-β1)group,curcu-min group,EZH2 overexpression group,EZH2 knockdown group and EZH2 inhibitor group.HSC-T6 cells in control group were cultured normally,HSC-T6 cells in TGF-β1 group was treated with TGF-β1,HSC-T6 cells in curcumin group were treated with TGF-β1 and curcumin,HSC-T6 cells in EZH2 overexpression group were treated with TGF-β1 and EZH2 eukaiyotic expression vector,HSC-T6 cells in EZH2 knockdown group were treated with TGF-β1 and EZH2 interfering RNA,and HSC-T6 cells in EZH2 inhibitor group were treated with TGF-β1 and EZH2 inhibitor DZNep.RNA and proteins were extracted,the expressions of liver fibrosis related genes α-smooth muscle actin(α-SM A),type I collagen a1(Col1a1),tissue inhibitor of metalloproteinase 1(Timp1),histone transmethylase EZH2 and liver fibrosis inhibitory factor PPARγ were detected by real-time PCR and Western blot,respectively.H3K27me3 level was detected by immunofluorescence.Results Compared with control group,the expressions of α-SMA,Col1 a1,Timp1,EZH2 were increased in TGF-β1 group(P<0.01),H3K27me3 level was increased,and the expression of PPARγ was decreased(P<0.01),while the results in curcumin group were opposite to those in TGF-β1 group(P<0.01 or P<0.05).Compared with TGF-β1 group,the expression of PPARγ was decreased in EZH2 overexpression group(P<0.05),while the PPARγ expression was increased in EZH2 knockdown group and EZH2 inhibitor group(P<0.05).Conclusion Curcumin can inhibit the expression of EHZ2,then increase PPARγ expression,thus suppressing HSCs activation.关键词
姜黄素/Zeste基因增强子同源物2/过氧化物酶体增殖物激活受体γ/肝星状细胞/转化生长因子-β1Key words
curcumin/enhancer of Zeste homolog 2/peroxisome proliferator-activated receptor γ/hepatic stellate cells/transforming growth factor-β1分类
医药卫生引用本文复制引用
史晓燕,潘萌..姜黄素通过EZH2/PPARγ途径抑制肝星状细胞活化[J].山西医科大学学报,2023,54(12):1577-1584,8.基金项目
国家自然科学基金青年科学基金项目(81704073) (81704073)
陕西省自然科学基础研究计划青年项目(2017JQ8018) (2017JQ8018)
陕西省重点研发计划一般项目(2022SF-225) (2022SF-225)