The inducible cAMP early repressor ICERIIγ inhibits CREB and AP-1 transcription but not AT1 receptor gene expression in vascular smooth muscle cells

Growth factors and agonists of both G alphas and G alphaq-coupled receptor agonists each down regulate angiotensin AT(1) receptor gene expression in vascular smooth muscle cells. To test whether the transcription factor CREB is in the pathway involved in modulation of AT(1)-receptor gene expression, AT(1) receptor mRNA levels were measured after stimulation with forskolin, angiotensin II and PDGF-BB in VSMC expressing the inducible cAMP early repressor protein, ICERII gamma, fused to the green fluorescent protein (eGFP). This fusion protein inhibits luciferase induction from promoters driven by either CREB response elements (CRE) or, unexpectedly, by tetradecanoylphorbol acetate response elements (TRE), which bind activator protein (AP-1). EGFP-ICERII gamma expression inhibits occupancy of CRE and TRE elements by endogenous VSMC nuclear proteins. Nevertheless, agonist-induced AT(1)-receptor mRNA down regulation is unaffected by eGFP-ICERII gamma expression. Although CREB transcription is activated by multiple classes of agonists in VSMC, and ICER can inhibit agonist-induced transcription mediated by both CREB and AP-1 enhancers, these transcription factors are not obligate components of the pathways regulating AT(1)-R gene expression in rat VSMC.