cAMP inhibits TGFbeta1-induced in vitro angiogenesis.
FEBS Lett
; 569(1-3): 105-11, 2004 Jul 02.
Article
en En
| MEDLINE
| ID: mdl-15225617
ABSTRACT
Transforming growth factor-beta (TGFbeta1) is a proangiogenic factor both, in vitro and in vivo, that is mainly involved in the later phases of angiogenesis. In an attempt to identify genes that participate in this effect, we found that TGFbeta1 down-regulates expression of adenylate cyclase VI. In addition, cAMP analogs (8-Bromo-cAMP) and forskolin (an adenylate cyclase activator) also reduced TGFbeta1-induced in vitro angiogenesis in mouse endothelial cell lines and in primary cultures of human umbilical vein endothelial cells on collagen gels. Induction of Ets-1 and plasminogen activator inhibitor-1 (PAI-1) by TGFbeta1 was blocked by these cAMP agonists and activators, in the absence of effects on endothelial cell viability. Moreover, the signal transduction pathways stimulated by TGFbeta1 were unaffected. Thus, Smad2 was normally phosphorylated and translocated to the nucleus in the presence of forskolin. In contrast, transfection studies using the PAI-1-promoter indicated that these cAMP analogues inhibit transcriptional stimulation by TGFbeta1. Electrophoretic mobility shift assay showed that Smad2/3 were bound normally to a TGFbeta1-response region in the presence of the cAMP analogs. In all, these data suggest that the cAMP pathway inhibits the transcriptional activity of Smads, that could be responsible for the block of the TGFbeta1-induced in vitro angiogenesis caused by this second messenger.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
8-Bromo Monofosfato de Adenosina Cíclica
/
Endotelio Vascular
/
Factor de Crecimiento Transformador beta
/
AMP Cíclico
/
Neovascularización Fisiológica
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
FEBS Lett
Año:
2004
Tipo del documento:
Article
País de afiliación:
España