Abstract
Fibronectin seems to play an important role in promoting the characteristic changes of vascular smooth muscle cells in diabetes mellitus including overexpression of the platelet-derived growth factor beta-receptor. To determine the regulatory mechanism of the beta-receptor by fibronectin, we have analyzed the effect of fibronectin on the expression of the beta-receptor in cultured rat aortic smooth muscle cells using the beta-receptor promoter/luciferase expression vector system. Fibronectin was found to stimulate the expression of the beta-receptor at the transcriptional level. Both a MEK1 inhibitor PD98059 and a tyrosine kinase inhibitor herbimycin A significantly inhibited the fibronectin-stimulated receptor transcription. Herbimycin A also completely inhibited the fibronectin-stimulated increase in tyrosine phosphorylation of focal adhesion kinase. These data suggest the involvement of the integrin-mediated mitogen-activated protein kinase pathway downstream of fibronectin stimulation in the activation process of the beta-receptor promoter.
Copyright 1998 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aorta / cytology
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Aorta / drug effects
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Benzoquinones
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Dose-Response Relationship, Drug
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Fibronectins / pharmacology*
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Flavonoids / pharmacology
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Genes, Reporter
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Integrins / metabolism
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Lactams, Macrocyclic
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Luciferases / biosynthesis
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Luciferases / genetics
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Muscle, Smooth, Vascular / drug effects*
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Promoter Regions, Genetic
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Protein Kinase Inhibitors
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Quinones / pharmacology
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Rats
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Receptor, Platelet-Derived Growth Factor beta
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Receptors, Platelet-Derived Growth Factor / biosynthesis*
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Receptors, Platelet-Derived Growth Factor / genetics
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Recombinant Fusion Proteins / biosynthesis
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Rifabutin / analogs & derivatives
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Signal Transduction
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Transcription, Genetic
Substances
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Benzoquinones
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Fibronectins
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Flavonoids
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Integrins
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Lactams, Macrocyclic
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Protein Kinase Inhibitors
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Quinones
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Recombinant Fusion Proteins
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Rifabutin
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herbimycin
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Luciferases
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Receptor, Platelet-Derived Growth Factor beta
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Receptors, Platelet-Derived Growth Factor
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Calcium-Calmodulin-Dependent Protein Kinases
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one