title: The inducible cAMP early repressor ICERIIgamma inhibits CREB and AP-1 transcription but not AT1 receptor gene expression in vascular smooth muscle cells.
abstract: Growth factors and agonists of both G alpha s and G alpha q-coupled receptor agonists each down regulate angiotensin AT1 receptor gene expression in vascular smooth muscle cells. To test whether the transcription factor CREB is in the pathway involved in modulation of AT1-receptor gene expression, AT1 receptor mRNA levels were measured after stimulation with forskolin, angiotensin II and PDGF-BB in VSMC expressing the inducible cAMP early repressor protein, ICERIIgamma, 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-ICERIIgamma expression inhibits occupancy of CRE and TRE elements by endogenous VSMC nuclear proteins. Nevertheless, agonist-induced AT1-receptor mRNA down regulation is unaffected by eGFP-ICERIIgamma 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 AT1-R gene expression in rat VSMC.
authors: Department of Pharmacology, Emory University School of Medicine, and Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, GA 30322, USA.
authors: X
authors: X
authors: Wang
authors: T J
authors: TJ
authors: Murphy
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic; D000077214:Becaplermin; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D051786:Cyclic AMP Response Element Modulator; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics*; D012097:Repressor Proteins / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D012097:Repressor Proteins; D018808:Transcription Factor AP-1; D000804:Angiotensin II; D051786:Cyclic AMP Response Element Modulator; D000077214:Becaplermin; D005576:Colforsin; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate