DeltaEF1 mediates TGF-beta signaling in vascular smooth muscle cell differentiation.
Dev Cell
; 11(1): 93-104, 2006 Jul.
Article
em En
| MEDLINE
| ID: mdl-16824956
ABSTRACT
Alteration in the differentiated state of smooth muscle cells (SMCs) is known to be integral to vascular development and the pathogenesis of vascular disease. However, it is still largely unknown how environmental cues translate into transcriptional control of SMC genes. We found that deltaEF1 is upregulated during SMC differentiation and selectively transactivates the promoters of SMC differentiation marker genes, SM alpha-actin and SM myosin heavy chain (SM-MHC). DeltaEF1 physically interacts with SRF and Smad3, resulting in a synergistic activation of SM alpha-actin promoter. Chromatin immunoprecipitation assays and knockdown experiments showed that deltaEF1 is involved in the control of the SMC differentiation programs induced by TGF-beta signaling. Overexpression of deltaEF1 inhibited neointima formation and promoted SMC differentiation, whereas heterozygous deltaEF1 knockout mice exhibited exaggerated neointima formation. It thus appears deltaEF1 mediates SMC differentiation via interaction with SRF and Smad3 during development and in vascular disease.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Fator de Crescimento Transformador beta
/
Proteínas de Homeodomínio
/
Músculo Liso Vascular
Limite:
Animals
Idioma:
En
Revista:
Dev Cell
Assunto da revista:
EMBRIOLOGIA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Japão