Inhibitory Effect of Emodin on Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) Expression in Rat Hepatic Stellate Cells
| Autor: | Jun-Ping Zhang, Peng Sun, Zhen Yu Xiao, Min Gui, Shuo Feng Wang, Jian Feng Dai, Yao Cheng Rui, Yue Fan Zhang |
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| Rok vydání: | 2006 |
| Předmět: |
Transcriptional Activation
Emodin Physiology Blotting Western Electrophoretic Mobility Shift Assay Biology Mice chemistry.chemical_compound Transforming Growth Factor beta Animals Humans Electrophoretic mobility shift assay Enzyme Inhibitors Phosphorylation Extracellular Signal-Regulated MAP Kinases Protein kinase A Cells Cultured Tissue Inhibitor of Metalloproteinase-1 Reverse Transcriptase Polymerase Chain Reaction Kinase Gastroenterology Molecular biology Rats Reverse transcription polymerase chain reaction Liver chemistry Hepatic stellate cell Signal transduction Signal Transduction Transforming growth factor |
| Zdroj: | Digestive Diseases and Sciences. 52:200-207 |
| ISSN: | 1573-2568 0163-2116 |
| DOI: | 10.1007/s10620-006-9321-z |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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