REGULATION 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 t he regulation of IGFBPs in human aorta smooth muscle cells by cyclic A MP, dexamethasone and IGF-I. cAMP decreased IGFBP-3, increased IGFBP-4 and increased IGFBP-6. Dexamethasone decreased IGFBP-3, slightly incr eased lGFBP-4 and increased IGFBP-6. IGF-I increased IGFBP-3 and IGFBP -6 while decreasing IGFBP-4. Co-incubation with IGF-I and dexamethason e 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 surf ace-bound IGFBP-3. In cells incubated with cAMP and IGF-I, media IGFBP -4 was decreased, despite increased IGFBP-4 mRNA, in this case seconda ry to the dominant effect of IGF-I-stimulated lGFBP-4 protease. These findings suggest that cAMP, dexamethasone and IGF-I regulate IGFBP pro duction in human aorta smooth muscle cells via a complex interplay of changes in transcription, protease activation and dissociation of cell surface-bound IGFBPs. (C) 1998 Churchill Livingstone.