Differential response of mesoderm- and neural crest-derived smooth muscle to TGF-beta1: regulation of c-myb and alpha1 (I) procollagen genes.
Exp Cell Res
; 230(2): 169-80, 1997 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-9024776
ABSTRACT
Previously, we demonstrated that avian vascular smooth muscle cells (VSMC) derived from embryonic abdominal and thoracic aorta grow differently in the presence of transforming growth factor beta (TGF-beta1) and platelet-derived growth factor (PDGF-BB) (Wrenn et al., In Vitro Cell. Dev. Biol. 29, 73-78, 1992). The thoracic VSMC (N-VSMC) are derived from neural crest, and therefore differentiate from ectoderm; the abdominal VSMC (M-VSMC) are derived from mesoderm. The present study was designed to identify factors that mediate the differential responses of the VSMC to TGF-beta1. We found that TGF-beta1 increased DNA synthesis by approximately sevenfold in N-VSMC. Levels of both alpha1 (I) procollagen and c-myb mRNAs were markedly induced in N-VSMC treated with TGF-beta1. Chimeric plasmids containing up to 3.5 kb of alpha1 (I) procollagen 5' flanking DNA were induced to equivalent levels as procollagen mRNA in N-VSMC. However, TGF-beta1 increased DNA synthesis by threefold in M-VSMC; there was no effect on alpha1 (I) procollagen expression, and c-myb was not expressed, as demonstrated by immunohistochemistry staining and RNA analyses. Antisense c-myb oligodeoxynucleotides blocked the TGF-beta1 induction of alpha1 (I) procollagen and the growth of N-VSMC. The increase in DNA synthesis by M- and N-VSMC was correlated with the secretion of PDGF-AA, and staurosporine and antibodies directed against PDGF-AA suppressed DNA synthesis. Our results demonstrate that TGF-beta1 activity and c-myb expression modulate the expression of alpha1 (I) collagen and cell proliferation in neural crest-derived smooth muscle. The regulation of these events by TGF-beta1 may be important during morphogenesis of blood vessels and vascular diseases.
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Base de dados:
MEDLINE
Assunto principal:
Aorta Abdominal
/
Aorta Torácica
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Regulação da Expressão Gênica
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Proteínas Proto-Oncogênicas c-myc
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Fator de Crescimento Transformador beta
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Pró-Colágeno
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Vasos Coronários
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Músculo Liso Vascular
Idioma:
En
Ano de publicação:
1997
Tipo de documento:
Article