VEGF ameliorates tubulointerstitial fibrosis in unilateral ureteral obstruction mice via inhibition of epithelial-mesenchymal transition.
Acta Pharmacol Sin
; 32(12): 1513-21, 2011 Dec.
Article
em En
| MEDLINE
| ID: mdl-21986574
ABSTRACT
AIM:
Vascular endothelial growth factor (VEGF) has been shown to be a survival factor for renal tubular epithelial cells. In the present study, we investigated whether administration of VEGF ameliorates tubulointerstitial fibrosis in a mouse model of unilateral ureteral obstruction (UUO).METHODS:
Thirty-six male CD-1 mice were randomly divided into three groups sham-operation, UUO and UUO+VEGF group. VEGF (50 µg/kg) was subcutaneously injected twice daily from d 1 to d 14. Mice in each group were killed at d 3, 7, or 14 after the operation, and the tubulointerstitial fibrosis was histopathologically evaluated. Human proximal tubular epithelial cells (HK-2) were used for in vitro study. The expression levels of α-SMA, E-cadherin, TGF-ß1, CTGF, and BMP-7 in the kidney were determined using Western blot and RT-PCR.RESULTS:
In the UUO mice, the degree of interstitial fibrosis was dramatically increased in a time-dependent manner. At d 3, 7, and 14, both the mRNA and protein expression levels for α-SMA, TGF-ß1, and CTGF were significantly upregulated, whereas those for E-cadherin and BMP-7 were significantly downregulated. At d 3 and 7, VEGF treatment significantly reduced interstitial fibrosis and the expression levels for α-SMA, TGF-ß1, and CTGF, while significantly increased the expression of E-cadherin and BMP-7, as compared with the UUO mice. At d 14 after operation, no significant differences were observed in the expression of the examined markers between VEGF-treated mice and UUO mice, with the exception of CTGF. In HK-2 cells, VEGF blocked TGF-ß1-induced α-SMA and vimentin expression and restored E-cadherin expression in a dose-dependent manner.CONCLUSION:
VEGF may ameliorate renal tubulointerstitial fibrosis at the early stage in UUO mice. This effect may be related to inhibition of VEGF on renal tubular epithelial-mesenchymal transition (EMT).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Obstrução Ureteral
/
Fibrose
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Fator A de Crescimento do Endotélio Vascular
/
Transição Epitelial-Mesenquimal
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Acta Pharmacol Sin
Ano de publicação:
2011
Tipo de documento:
Article