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All rights reserved. http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAbG0fx1-higb6HW5zYZwvsK3bMg40M1B84WWzV84AuBs#_5 http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/version 20131211 http://www.tkuhn.ch/bel2nanopub/RAbG0fx1-higb6HW5zYZwvsK3bMg40M1B84WWzV84AuBs#_4 http://www.w3.org/ns/prov#value Endothelin-1 is not only a powerful vasoconstrictor but also a potent mitogen for vascular smooth muscle cells (SMC), acting through both the endothelin-A and endothelin-B receptor (ET(B)-R). Although vascular SMC are known to express the ET(B)-R, its transcriptional regulation has not been studied thus far. Here we demonstrate that the potent inhibitor of nuclear factor kappaB activation, pyrrolidine dithiocarbamate (PDTC; 30-100 microM), induces de novo ET(B)-R expression in rat aortic and mesenteric cultured SMC. Electrophoretic mobility shift analyses revealed that besides inhibition of nuclear factor kappaB, PDTC enhances activator protein-1 (AP-1), CCAAT/enhancer-binding protein (C/EBP), and GATA-2 activity in these cells. Preincubation of PDTC-stimulated cells with appropriate decoy oligodeoxynucleotides confirmed the involvement of these three transcription factors, namely that of AP-1, in ET(B)-R expression. The stimulatory effect of PDTC on ET(B)-R expression was also confirmed functionally by monitoring an enhanced ET-1-induced apoptosis in PDTC-treated cells that was sensitive to the ET(B)-R antagonist, BQ788. Taken together, these findings demonstrate that C/EBP, GATA-2, and in particular AP-1 can control ET(B)-R expression in vascular SMC. They further support the notion that ET(B)-R expression in these cells may play an important role in cardiovascular complications, such as restenosis following angioplasty that in the early phase is characterized by prominent SMC apoptosis. http://www.tkuhn.ch/bel2nanopub/RAbG0fx1-higb6HW5zYZwvsK3bMg40M1B84WWzV84AuBs#_4 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/11093771 http://www.tkuhn.ch/bel2nanopub/RAbG0fx1-higb6HW5zYZwvsK3bMg40M1B84WWzV84AuBs#_5 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAbG0fx1-higb6HW5zYZwvsK3bMg40M1B84WWzV84AuBs#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/11093771 http://www.tkuhn.ch/bel2nanopub/RAbG0fx1-higb6HW5zYZwvsK3bMg40M1B84WWzV84AuBs#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAbG0fx1-higb6HW5zYZwvsK3bMg40M1B84WWzV84AuBs#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAbG0fx1-higb6HW5zYZwvsK3bMg40M1B84WWzV84AuBs#_4 http://www.tkuhn.ch/bel2nanopub/RAbG0fx1-higb6HW5zYZwvsK3bMg40M1B84WWzV84AuBs#pubinfo http://www.tkuhn.ch/bel2nanopub/RAbG0fx1-higb6HW5zYZwvsK3bMg40M1B84WWzV84AuBs http://purl.org/dc/terms/created 2014-07-03T14:31:38.235+02:00 http://www.tkuhn.ch/bel2nanopub/RAbG0fx1-higb6HW5zYZwvsK3bMg40M1B84WWzV84AuBs http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAbG0fx1-higb6HW5zYZwvsK3bMg40M1B84WWzV84AuBs http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234