title: Inhibitory effect of emodin on tissue inhibitor of metalloproteinases-1 (TIMP-1) expression in rat hepatic stellate cells.
abstract: Emodin inhibited expression of both transforming growth factor beta1 (TGFbeta1)- 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 TGFbeta1-induced p42/p44 mitogen-activated protein kinase phosphorylation but did not alter PMA induction. We conclude that emodin effectively inhibits PMA- and TGFbeta1-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.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Guo He Road 325, Shanghai 200433, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Gui
authors.forename: Yue Fan
authors.initials: YF
authors.lastname: Zhang
authors.forename: Zhen Yu
authors.initials: ZY
authors.lastname: Xiao
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.forename: Jian Feng
authors.initials: JF
authors.lastname: Dai
authors.forename: Shuo Feng
authors.initials: SF
authors.lastname: Wang
authors.forename: Yao Cheng
authors.initials: YC
authors.lastname: Rui
authors.forename: Jun Ping
authors.initials: JP
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D004642:Emodin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology*; D051379:Mice; D010766:Phosphorylation; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D048049:Extracellular Signal-Regulated MAP Kinases; D004642:Emodin