Mechanisms of TGF-ß-induced differentiation in human vascular smooth muscle cells.
J Vasc Res
; 48(6): 485-94, 2011.
Article
em En
| MEDLINE
| ID: mdl-21832838
ABSTRACT
BACKGROUND:
Transforming growth factor-ß (TGF-ß) plays an important role in vascular homeostasis through effects on vascular smooth muscle cells (SMC). Fine-tuning of TGF-ß signaling occurs at the level of ALK receptors or Smads, and is regulated with cell type specificity.METHODS:
Our goal was to understand TGF-ß signaling in regulating SMC differentiation marker expression in human SMC. Activation of Smads was characterized, and loss- and gain-of-function reagents used to define ALK pathways. In addition, Smad-independent mechanisms were determined.RESULTS:
TGF-ß type I receptors, ALK1 and ALK5, are expressed in human SMC, and TGF-ß1 phosphorylates Smad1/5/8 and Smad2/3 in a time- and dosage-dependent pattern. ALK5 activity, not bone morphogenetic protein type I receptors, is required for Smad phosphorylation. Endoglin, a TGF-ß type III receptor, is a TGF-ß1 target in SMC, yet endoglin does not modify TGF-ß1 responsiveness. ALK5, not ALK1, is required for TGF-ß1-induction of SMC differentiation markers, and ALK5 signals through an ALK5/Smad3- and MAP kinase-dependent pathway.CONCLUSION:
The definition of the specific signaling downstream of TGF-ß regulating SMC differentiation markers will contribute to a better understanding of vascular disorders involving changes in SMC phenotype.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Fator de Crescimento Transformador beta1
/
Músculo Liso Vascular
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article