Inhibitory effect of emodin on tissue inhibitor of metalloproteinases-1 (TIMP-1) expression in rat hepatic stellate cells

• Published in: Digestive diseases and sciences Vol. 52; no. 1; pp. 200 - 207
• Main Authors: Gui, Min, Zhang, Yue Fan, Xiao, Zhen Yu, Sun, Peng, Dai, Jian Feng, Wang, Shuo Feng, Rui, Yao Cheng, Zhang, Jun Ping
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 2007; Springer Nature B.V
• Subjects: Animals; Biological and medical sciences; Blotting, Western; Cells, Cultured; Electrophoretic Mobility Shift Assay; Emodin - pharmacology; Enzyme Inhibitors - pharmacology; Extracellular Signal-Regulated MAP Kinases - metabolism; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Kinases; Liver - cytology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Mice; Other diseases. Semiology; Phosphorylation; Rats; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - drug effects; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Transcriptional Activation - drug effects; Transforming Growth Factor beta - metabolism; Spider cell; Hepatic fibrosis; Rat; Enzyme; Transferases; Rodentia; Hepatic disease; Extracellular; Emodin, Tissue inhibitor of metalloproteinase-1, Hepatic stellate cells; Vertebrata; Regulation(control); Mammalia; Kinase; Protein kinase; Animal; Digestive diseases; Activator protein-1· Extracellular signal-regulated kinase, Hepatic fibrosis
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-006-9321-z

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.