title: VEGF ameliorates tubulointerstitial fibrosis in unilateral ureteral obstruction mice via inhibition of epithelial-mesenchymal transition.
abstract: OBJECTIVE
  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-β1, 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-β1, 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-β1, 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-β1-induced α-SMA and vimentin expression and restored E-cadherin expression in a dose-dependent manner.
  
  
  CONCLUSIONS
  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).
authors: Division of Nephrology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.
authors: Yao-guo
authors: YG
authors: Lian
authors: Qiu-gen
authors: QG
authors: Zhou
authors: Ying-juan
authors: YJ
authors: Zhang
authors: Fa-lei
authors: FL
authors: Zheng
mesh_terms: D000818:Animals; D058750:Epithelial-Mesenchymal Transition; D005355:Fibrosis / Q000517:prevention & control*; D006801:Humans; D008297:Male; D051379:Mice; D014517:Ureteral Obstruction / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
chemical_list: D042461:Vascular Endothelial Growth Factor A