Abstract
We found that the expression of galectin-1 and galectin-3 was significantly up-regulated in hepatic stellate cells (HSCs) both in the course of their transdifferentiation into myofibroblasts, a process of "self-activation," and in the fibrosis of liver tissues. Recombinant galectin-1 and galectin-3 stimulated the proliferation of cultured HSCs via the MEK1/2-ERK1/2 signaling pathway. However, galectin-3 utilized protein kinases C and A to induce this process, whereas galectin-1 did not. We also found that thiodigalactoside, a potent inhibitor of beta-galactoside binding, attenuated the effects of both galectins. In addition, galectin-1, but not galectin-3, promoted the migration of HSCs. Thus, it appears that galectin-1 and galectin-3, generated by activated HSCs, could participate in beta-galactoside binding and induce different intracellular signaling pathways leading to the proliferation of HSCs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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Cell Division / drug effects*
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Cell Movement / drug effects
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Cells, Cultured
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Endothelium, Vascular / chemistry
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Enzyme Inhibitors / pharmacology
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Galectin 1 / genetics
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Galectin 1 / pharmacology
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Galectin 1 / physiology*
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Galectin 3 / genetics
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Galectin 3 / pharmacology
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Galectin 3 / physiology*
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Gene Expression
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Hepatocytes / chemistry
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Humans
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Kupffer Cells / chemistry
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Liver / cytology*
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MAP Kinase Kinase 1
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MAP Kinase Kinase 2
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Male
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / metabolism
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Phosphorylation
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Protein Kinase Inhibitors
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / antagonists & inhibitors
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RNA, Messenger / analysis
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Rats
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Rats, Wistar
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Recombinant Proteins / pharmacology
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction*
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beta-Galactosidase / metabolism
Substances
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Enzyme Inhibitors
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Galectin 1
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Galectin 3
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Protein Kinase Inhibitors
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RNA, Messenger
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Recombinant Proteins
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MAP2K2 protein, human
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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Cyclic AMP-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 1
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MAP Kinase Kinase 2
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MAP2K1 protein, human
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Mitogen-Activated Protein Kinase Kinases
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beta-Galactosidase