Regulations of IGF binding proteins in human aorta vascular smooth muscle cells by cAMP, dexamethasone and IGF-I.
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.
Hayford
K
K
Department of Internal Medicine, Veterans Administration Medical Center, The University of Iowa, Iowa City 52246, USA.
Boes
M
M
Dake
B L
BL
Bar
R S
RS
D001011:Aorta / Q000166:cytology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008666:Metalloendopeptidases / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011266:Pregnancy-Associated Plasma Protein-A
D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D018976:Insulin-Like Growth Factor Binding Protein 6; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D000242:Cyclic AMP; D008666:Metalloendopeptidases; D011266:Pregnancy-Associated Plasma Protein-A