Relationship between the effect of vascular endothelial growth factor on epithelial-mesenchymal transition of HK-2 cells and the expressions of bone morphogenetic protein-7 and inhibitor of DNA binding/differentiation / 中国医学科学院学报
Acta Academiae Medicinae Sinicae
;
(6): 703-710, 2008.
Artigo
em Chinês
| WPRIM
| ID: wpr-259097
ABSTRACT
<p><b>OBJECTIVE</b>To examine the relationship between effect of vascular endothelial growth factor (VEGF) on epithelial-myofibroblast transition (EMT) of HK-2 cells and changes in expressions of bone morphogenetic protein-7 (BMP-7) and inhibitor of DNA binding/differentiation (Id) 2, Id3.</p><p><b>METHODS</b>The cultured HK-2 cells were co-treated with transforming growth factor-beta1 (TGF-beta1) (5 ng/ml) and VEGF165 (0.1, 1, 10, 100 ng/ml), or with TGF-beta1 (5 ng/ml) and VEGF receptor-1 neutralized antibody (10 microg/ ml), and were also co-treated with TGF-beta1 (5 ng/ml) and VEGF165 (100 ng/ml) with or without activin receptor-like kinase 6 (Alk6)/Fc Chimera (2 microg/ml, to neutralize endogenous BMP-7) for 48 hours. mRNA and protein expressions of alpha-smooth muscle actin (alpha-SMA), E-cadherin, BMP-7, Id2 and Id3 of HK-2 cells were assessed with double-stain immunocytochemistry, real-time PCR and Western blot respectively.</p><p><b>RESULTS</b>Compared with normal controls, alpha-SMA expression significantly increased, while E-cadherin, BMP-7, Id2, and Id3 mRNA and protein expressions markedly decreased in HK-2 cells treated with TGF-beta1 (5 ng/ml) (P < 0.05). VEGF165 interrupted TGF-beta1 induced alpha-SMA expression in a dose-dependent manner and upregulated BMP-7, Id2 mRNA and protein expressions of the cells (P < 0.05). alpha-SMA expression increased, while E-cadherin, BMP-7, and Id2 expressions decreased further in HK-2 cells co-treated with TGF-beta1 and VEGFR1 antibody compared with normal controls (P < 0.05). When endogenous BMP-7 was neutralized with Alk6/Fc Chimera in the cells co-treated with TGF-beta1 and VEGF165, alpha-SMA expression upregulated (P < 0.05), while Id2 was not changed.</p><p><b>CONCLUSIONS</b>VEGF165 may partially inhibit TGF-beta1-induced EMT of HK-2 cells in vitro. This effect is related to the upregulated expressions of BMP-7 and Id2. Id2 may be upregulated directly by VEGF165, but not related to BMP-7.</p>
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Diferenciação Celular
/
Linhagem Celular
/
Regulação da Expressão Gênica
/
Biologia Celular
/
Fator A de Crescimento do Endotélio Vascular
/
Células Epiteliais
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Proteínas Inibidoras de Diferenciação
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Proteína 2 Inibidora de Diferenciação
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Fator de Crescimento Transformador beta1
/
Proteína Morfogenética Óssea 7
Limite:
Humanos
Idioma:
Chinês
Revista:
Acta Academiae Medicinae Sinicae
Ano de publicação:
2008
Tipo de documento:
Artigo
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