Abstract
Human vascular smooth muscle cells produce IGFBP-3, IGFBP-4, IGFBP-6 and proteases specific for IGFBP-3 and IGFBP-4. This study evaluated the regulation of IGFBPs in human aorta smooth muscle cells by cyclic AMP, dexamethasone and IGF-I. cAMP decreased IGFBP-3, increased IGFBP-4 and increased IGFBP-6. Dexamethasone decreased IGFBP-3, slightly increased IGFBP-4 and increased IGFBP-6. IGF-I increased IGFBP-3 and IGFBP-6 while decreasing IGFBP-4. Co-incubation with IGF-I and dexamethasone or cAMP increased media IGFBP-3, despite a decrease in IGFBP-3 mRNA, due to the dominant effect of IGF-I-induced dissociation of cell surface-bound IGFBP-3. In cells incubated with cAMP and IGF-I, media IGFBP-4 was decreased, despite increased IGFBP-4 mRNA, in this case secondary to the dominant effect of IGF-I-stimulated IGFBP-4 protease. These findings suggest that cAMP, dexamethasone and IGF-I regulate IGFBP production in human aorta smooth muscle cells via a complex interplay of changes in transcription, protease activation and dissociation of cell surface-bound IGFBPs.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aorta / cytology
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Cells, Cultured
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Cyclic AMP / pharmacology*
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Dexamethasone / pharmacology*
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Humans
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Insulin-Like Growth Factor Binding Protein 3 / drug effects
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Insulin-Like Growth Factor Binding Protein 3 / genetics
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Insulin-Like Growth Factor Binding Protein 3 / metabolism
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Insulin-Like Growth Factor Binding Protein 4 / drug effects
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Insulin-Like Growth Factor Binding Protein 4 / genetics
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Insulin-Like Growth Factor Binding Protein 4 / metabolism
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Insulin-Like Growth Factor Binding Protein 6 / drug effects
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Insulin-Like Growth Factor Binding Protein 6 / genetics
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Insulin-Like Growth Factor Binding Protein 6 / metabolism
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Insulin-Like Growth Factor Binding Proteins / drug effects
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Insulin-Like Growth Factor Binding Proteins / genetics
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Insulin-Like Growth Factor Binding Proteins / metabolism*
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Insulin-Like Growth Factor I / pharmacology*
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Metalloendopeptidases / drug effects
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Metalloendopeptidases / metabolism
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Muscle, Smooth, Vascular / cytology
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / metabolism*
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Pregnancy-Associated Plasma Protein-A
Substances
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Insulin-Like Growth Factor Binding Protein 3
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Insulin-Like Growth Factor Binding Protein 4
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Insulin-Like Growth Factor Binding Protein 6
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Insulin-Like Growth Factor Binding Proteins
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Insulin-Like Growth Factor I
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Dexamethasone
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Cyclic AMP
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Metalloendopeptidases
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Pregnancy-Associated Plasma Protein-A