Abstract
We reported in this manuscript that TGF-beta1 induces apoptosis in AML12 murine hepatocytes, which is associated with the activation of p38 MAPK signaling pathway. SB202190, a specific inhibitor of p38 MAPK, strongly inhibited the TGF-beta1-induced apoptosis and PAI-1 promoter activity. Treatment of cells with TGF-beta1 activates p38. Furthermore, over-expression of dominant negative mutant p38 also reduced the TGF-beta1-induced apoptosis. The data indicate that the activation of p38 is involved in TGF-beta1-mediated gene expression and apoptosis.
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 / drug effects
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Apoptosis / physiology*
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Cells, Cultured / drug effects
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DNA Fragmentation / drug effects
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DNA Fragmentation / physiology
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Enzyme Inhibitors / pharmacology
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Gene Expression Regulation, Enzymologic / drug effects
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Gene Expression Regulation, Enzymologic / physiology
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Genes, Reporter / drug effects
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Genes, Reporter / physiology
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Genetic Vectors / drug effects
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Genetic Vectors / physiology
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Hepatocytes / cytology
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Hepatocytes / drug effects
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Hepatocytes / metabolism*
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Imidazoles / pharmacology
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MAP Kinase Signaling System / drug effects
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MAP Kinase Signaling System / physiology*
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Mice
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Mitogen-Activated Protein Kinases / drug effects
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / metabolism*
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Mutation / drug effects
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Mutation / physiology
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Phosphorylation / drug effects
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Plasminogen Activator Inhibitor 1 / genetics
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Pyridines / pharmacology
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Transfection
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Transforming Growth Factor beta / metabolism*
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Transforming Growth Factor beta / pharmacology
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Transforming Growth Factor beta1
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p38 Mitogen-Activated Protein Kinases
Substances
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Enzyme Inhibitors
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Imidazoles
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Plasminogen Activator Inhibitor 1
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Pyridines
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Tgfb1 protein, mouse
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Transforming Growth Factor beta
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Transforming Growth Factor beta1
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole