Transglutaminase 2 promotes PDGF-mediated activation of PDGFR/Akt1 and ß-catenin signaling in vascular smooth muscle cells and supports neointima formation.
J Vasc Res
; 51(6): 418-28, 2014.
Article
em En
| MEDLINE
| ID: mdl-25612735
ABSTRACT
BACKGROUND:
Phenotypic switch of vascular smooth muscle cells (VSMCs) accompanies neointima formation and associates with vascular diseases. Platelet-derived growth factor (PDGF)-induced activation of PDGFR/Akt1 and ß-catenin signaling pathways in VSMCs has been implicated in vessel occlusion. Transglutaminase 2 (TG2) regulates these pathways and its levels are increased in the neointima.OBJECTIVE:
The aim of this study was to evaluate the role of TG2 in PDGF/ß-catenin signaling cross-talk and assess its contribution to neointima.METHODS:
Aortic VSMCs from wild-type and TG2 knockout mice were tested in vitro for levels of VSMC markers, proliferation, migration and PDGF-induced activation of PDGFR/Akt1 and ß-catenin pathways. Neointima in these mice was studied ex vivo in coronary vessels using a heart slice model and in vivo using a carotid artery ligation model.RESULTS:
Genetic deletion of TG2 attenuated the PDGF-induced phenotypic switch of aortic VSMCs, reduced their proliferation and migration rates, and inhibited PDGF-induced activation of PDGFR/Akt1 and ß-catenin pathways in both ex vivo and in vivo neointima models. Importantly, genetic deletion of TG2 also markedly attenuated vessel occlusion.CONCLUSIONS:
TG2 promotes neointima formation by mediating the PDGF-induced activation of the PDGFR/Akt1 and ß-catenin pathways in VSMCs. This study identifies TG2 as a potential therapeutic target for blocking neointima in blood vessels.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Transglutaminases
/
Estenose das Carótidas
/
Receptores do Fator de Crescimento Derivado de Plaquetas
/
Proteínas de Ligação ao GTP
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Proteínas Proto-Oncogênicas c-sis
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Estenose Coronária
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Miócitos de Músculo Liso
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Proteínas Proto-Oncogênicas c-akt
/
Beta Catenina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article