Differential roles of JNK, ERK1/2, and p38 mitogen-activated protein kinases on endothelial cell tissue repair functions in response to tumor necrosis factor-α.
J Vasc Res
; 50(2): 145-56, 2013.
Article
em En
| MEDLINE
| ID: mdl-23258237
ABSTRACT
Tumor necrosis factor (TNF)-α can alter tissue repair functions in a variety of cells including endothelial cells. However, the mechanism by which TNF-α mediates these functional changes has not fully been studied. We investigated the role of mitogen-activated protein kinases (MAPKs) on mediating the regulatory effect of TNF-α on the tissue repair functions of human pulmonary artery endothelial cells (HPAECs). TNF-α protected HPAECs from undergoing apoptosis induced by serum and growth factor deprivation, augmented collagen gel contraction, and stimulated wound closure. TNF-α activated c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and p38. Inhibitors of JNK (SP600125, 5 µM) or ERK1/2 (PD98059, 5 µM) significantly inhibited TNF-α-stimulated cell survival, contraction of collagen gels, and wound closure. In contrast, the p38 inhibitor SB203580 (5 µM) further amplified all of the TNF-α effects on HPAECs. TNF-α specifically activated p38α but not other p38 isoforms and suppression of p38α by an siRNA resulted in further amplification of the TNF-α effect. These results suggest that TNF-α stimulates tissue repair functions of HPAECs, and this may be mediated, at least in part, positively via JNK and ERK1/2, and negatively through p38α. MAPKs may play a role in endothelial cell-mediated tissue repair, especially in an inflammatory milieu where TNF-α is present.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artéria Pulmonar
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Cicatrização
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Endotélio Vascular
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Fator de Necrose Tumoral alfa
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Proteína Quinase 1 Ativada por Mitógeno
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Sistema de Sinalização das MAP Quinases
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Células Endoteliais
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Proteína Quinase 3 Ativada por Mitógeno
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Proteína Quinase 8 Ativada por Mitógeno
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Proteínas Quinases p38 Ativadas por Mitógeno
Limite:
Humans
Idioma:
En
Revista:
J Vasc Res
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos