Down-regulation of perlecan expression contributes to the inhibition of rat cardiac microvascular endothelial cell proliferation induced by hypoxia / 生理学报
Acta Physiologica Sinica
; (6): 221-226, 2007.
Article
em En
| WPRIM
| ID: wpr-258666
Biblioteca responsável:
WPRO
ABSTRACT
Exposure of endothelial cells (ECs) to hypoxia leads to a decrease in EC proliferation. However, the mechanism by which hypoxia inhibits EC proliferation is unclear. Perlecan has been reported to play an important role in regulating EC proliferation. We hypothesized that perlecan was involved in the hypoxia-induced inhibition of EC proliferation. To test this hypothesis, rat cardiac microvascular ECs were cultured under normoxic or hypoxic conditions for 12 h and harvested for determination of perlecan mRNA expression using real-time reverse transcription-polymerase chain reaction (RT-PCR). The results showed that exposure of ECs to hypoxia for 12 h induced a decrease in perlecan mRNA expression (61.72%, P<0.05). Concomitantly, the down-regulation of endogenous perlecan induced by hypoxia or the neutralization of endogenous perlecan with anti-perlecan antibody significantly inhibited EC proliferation and responsiveness to basic fibroblast growth factor (bFGF), and decreased focal adhesion kinase (FAK) expression and extracellular signal-regulated kinase 1/2 (ERK1/2) activation. These data indicate that down-regulation of perlecan expression contributes to hypoxia-induced inhibition of rat cardiac microvascular EC proliferation by suppressing FAK-mediated and ERK1/2-dependent growth signals.
Texto completo:
1
Base de dados:
WPRIM
Assunto principal:
Oxigênio
/
Capilares
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RNA Mensageiro
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Hipóxia Celular
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Regulação para Baixo
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Células Cultivadas
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Ratos Sprague-Dawley
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Circulação Coronária
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Proteoglicanas de Heparan Sulfato
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Sistema de Sinalização das MAP Quinases
Limite:
Animals
Idioma:
En
Revista:
Acta Physiologica Sinica
Ano de publicação:
2007
Tipo de documento:
Article