Abstract
The transdifferentiation of hepatic stellate cells into myofibroblast-like cells and the proliferation of the transdifferentiated cells are controlled by TGF-beta1. Little is known about the intracellular signal transducers of TGF-beta1. In this paper we show that in cultured hepatic stellate cells TGF-beta1 induces activation of Ras, Raf-1, MEK and MAPK p42 and p44. The activation of MAPK depends on the activation of MEK. Our data exclude that the observed effects are mediated by a bFGF or PDGF autocrine loop.
MeSH terms
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Animals
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Calcium-Calmodulin-Dependent Protein Kinases / drug effects
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Enzyme Activation / drug effects
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Fibroblast Growth Factor 2 / metabolism
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Fibroblast Growth Factor 2 / pharmacology
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Liver / cytology*
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Liver / drug effects
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Liver / metabolism*
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MAP Kinase Kinase 1
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Male
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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 Kinase Kinases*
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Mitogen-Activated Protein Kinases*
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Platelet-Derived Growth Factor / metabolism
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Platelet-Derived Growth Factor / pharmacology
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Protein Serine-Threonine Kinases / drug effects
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Protein Serine-Threonine Kinases / metabolism
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Protein-Tyrosine Kinases / drug effects
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Protein-Tyrosine Kinases / metabolism
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Proto-Oncogene Proteins / drug effects
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-raf
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Rats
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Rats, Wistar
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Transforming Growth Factor beta / pharmacology*
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ras Proteins / drug effects
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ras Proteins / genetics
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ras Proteins / metabolism*
Substances
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Platelet-Derived Growth Factor
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Proto-Oncogene Proteins
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Transforming Growth Factor beta
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Fibroblast Growth Factor 2
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-raf
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Calcium-Calmodulin-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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Mitogen-Activated Protein Kinase Kinases
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ras Proteins