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Blood ; 107(6): 2322-9, 2006 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-16189269

RESUMO

Platelet-derived growth factor D-chain (PDGF-D) is the newest member of the PDGF family of mitogens and chemoattractants expressed in a wide variety of cell types, including vascular smooth muscle cells (SMCs). The molecular mechanisms regulating PDGF-D transcription are not known. Primer extension analysis mapped a single transcriptional start site to the ccAGCGC motif with several potential Ets motifs located upstream. Ets-1, but not Ets-1 bearing only the DNA-binding domain, activates the PDGF-D promoter and mRNA expression in SMCs. Ets site D3 ((-470)GGAT(-467)) is singly required for basal and Ets-1-inducible PDGF-D promoter-dependent expression. D3 supports the interaction of endogenous and recombinant Ets-1 and Sp1. Sp1, like Ets-1, induces PDGF-D transcription and mRNA expression, which is blocked by mutant Ets-1. H2O2 stimulates Ets-1, but not Sp1, and activates D3-dependent PDGF-D transcription. Ets-1 and Sp1 siRNA block peroxide-inducible PDGF-D expression. Angiotensin II (ATII) induction of PDGF-D and Ets-1 was blocked by prior incubation of the cells with PEG-catalase, but not BSA, indicating that ATII-inducible Ets-1 and PDGF-D expression is mediated via H2O2. Thus, 2 separate trans-acting factors regulate PDGF-D transcription, alone and in response to oxidative stress.


Assuntos
Angiotensina II/farmacologia , Peróxido de Hidrogênio/farmacologia , Linfocinas/genética , Fator de Crescimento Derivado de Plaquetas/genética , Proteína Proto-Oncogênica c-ets-1/fisiologia , Fator de Transcrição Sp1/fisiologia , Transcrição Gênica , Animais , Bovinos , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Músculo Liso Vascular/citologia , Estresse Oxidativo , Regiões Promotoras Genéticas , Proteína Proto-Oncogênica c-ets-1/genética , Ratos , Sítio de Iniciação de Transcrição
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