Inhibitory effect of emodin on tissue inhibitor of metalloproteinases-1 (TIMP-1) expression in rat hepatic stellate cells
Inhibitory effect of emodin on tissue inhibitor of metalloproteinases-1 (TIMP-1) expression in rat hepatic stellate cells
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DOI：
10.1007/s10620-006-9321-z
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发表时间：
2007-01-01
影响因子：
3.1
通讯作者：
Zhang, Jun Ping
中科院分区：
文献类型：
--
作者：
Gui, Min;Zhang, Yue Fan;Zhang, Jun Ping
通过蛋白质印迹和逆转录聚合酶链反应，大黄素抑制永生化大鼠肝星状细胞系 HSC-T6 中转化生长因子 β 1 (TGF β 1) 和佛波酯 (PMA) 诱导的金属蛋白酶组织抑制剂 1 (TIMP-1) 的表达。报告基因检测表明，大黄素可降低基础和 PMA 诱导的活化蛋白 1 (AP-1) 启动子活性。电泳迁移率变动分析表明，大黄素降低了 HSC-T6 细胞中 AP-1 DNA 的结合活性。 AP-1成分分析表明大黄素还减弱JunD mRNA的表达。此外，大黄素显着抑制TGFβ1诱导的p42/p44丝裂原激活蛋白激酶磷酸化，但不改变PMA诱导。我们得出结论，大黄素分别通过抑制 AP-1 信号通路和细胞外信号调节激酶激活，有效抑制 PMA 和 TGF β 1 刺激的肝星状细胞中 TIMP-1 的表达。这些数据为大黄素抗肝纤维化的细胞和分子机制提供了新的见解。
Emodin inhibited expression of both transforming growth factor beta 1 (TGF beta 1)- and phorbol ester (PMA)-induced tissue inhibitors of metalloproteinase-1 (TIMP-1) in an immortalized rat hepatic stellate cell line, HSC-T6, by Western blot and reverse transcription polymerase chain reaction. Reporter gene assays showed that emodin reduced both basal and PMA-induced activated protein-1 (AP-1) promoter activities. Electrophoretic mobility shift assay revealed that emodin reduced AP-1 DNA binding activities in HSC-T6 cells. AP-1 components analysis showed that emodin also attenuated JunD mRNA expression. Furthermore, emodin markedly inhibited TGF beta 1-induced p42/p44 mitogen-activated protein kinase phosphorylation but did not alter PMA induction. We conclude that emodin effectively inhibits PMA- and TGF beta 1-stimulated TIMP-1 expression in hepatic stellate cells by suppressing the AP-1 signaling pathway and extracellular signal-regulated kinase activation, respectively. These data provide new insight into the cellular and molecular mechanisms of emodin against liver fibrosis.