Advanced glycation end-products induce heparanase expression in endothelial cells by the receptor for advanced glycation end products and through activation of the FOXO4 transcription factor.
Mol Cell Biochem
; 354(1-2): 47-55, 2011 Aug.
Article
em En
| MEDLINE
| ID: mdl-21461610
As an endo-ß (1-4)-D: -glucuronidase, heparanase can specifically cleave carbohydrate chains of heparan sulfate (HS) and has been implicated in development of endothelial cells dsyfunction. The advanced glycation end products (AGEs) play a pivotal role in the pathology of diabetic complications. In the present study, we investigated the effect of AGE-bovine serum albumin (AGE-BSA) on heparanase expression in human microvascular endothelial cells (HMVECs) and the underlying molecular mechanisms. The results indicated that in vitro direct exposure of HMVECs to AGE-BSA (300, 1000, and 3000 µg/ml) could increase heparanase mRNA and protein expression in a dose and time-dependent manner. The effect of 1000 µg/ml AGE-BSA could be abolished by neutralization with antibody of the receptor for advanced glycation end products (RAGE). Moreover, pretreatment with inhibitors of nuclear factor-κB (NF-κB) or PI3-kinase did not affect heparanase expression induced by AGE-BSA. Nevertheless, small interference RNA (siRNA) for transcriptional factor FOXO4 could reduce the increase of heparanase expression in HMVECs induced by 1000 µg/ml AGE-BSA. These results suggest that AGEs could induce heparanase expression in HMVECs by RAGE and predominantly through activation of the FOXO4 transcription factor.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Soroalbumina Bovina
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Endotélio Vascular
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Receptores Imunológicos
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Produtos Finais de Glicação Avançada
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Células Endoteliais
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Glucuronidase
Limite:
Animals
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Humans
Idioma:
En
Revista:
Mol Cell Biochem
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
China