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VEGF ameliorates tubulointerstitial fibrosis in unilateral ureteral obstruction mice via inhibition of epithelial-mesenchymal transition.
Acta Pharmacol Sin. 2011 Dec; 32(12):1513-21.AP

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-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.

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).

Authors+Show Affiliations

Division of Nephrology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21986574

Citation

Lian, Yao-guo, et al. "VEGF Ameliorates Tubulointerstitial Fibrosis in Unilateral Ureteral Obstruction Mice Via Inhibition of Epithelial-mesenchymal Transition." Acta Pharmacologica Sinica, vol. 32, no. 12, 2011, pp. 1513-21.
Lian YG, Zhou QG, Zhang YJ, et al. VEGF ameliorates tubulointerstitial fibrosis in unilateral ureteral obstruction mice via inhibition of epithelial-mesenchymal transition. Acta Pharmacol Sin. 2011;32(12):1513-21.
Lian, Y. G., Zhou, Q. G., Zhang, Y. J., & Zheng, F. L. (2011). VEGF ameliorates tubulointerstitial fibrosis in unilateral ureteral obstruction mice via inhibition of epithelial-mesenchymal transition. Acta Pharmacologica Sinica, 32(12), 1513-21. https://doi.org/10.1038/aps.2011.111
Lian YG, et al. VEGF Ameliorates Tubulointerstitial Fibrosis in Unilateral Ureteral Obstruction Mice Via Inhibition of Epithelial-mesenchymal Transition. Acta Pharmacol Sin. 2011;32(12):1513-21. PubMed PMID: 21986574.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - VEGF ameliorates tubulointerstitial fibrosis in unilateral ureteral obstruction mice via inhibition of epithelial-mesenchymal transition. AU - Lian,Yao-guo, AU - Zhou,Qiu-gen, AU - Zhang,Ying-juan, AU - Zheng,Fa-lei, Y1 - 2011/10/10/ PY - 2011/10/12/entrez PY - 2011/10/12/pubmed PY - 2012/3/22/medline SP - 1513 EP - 21 JF - Acta pharmacologica Sinica JO - Acta Pharmacol Sin VL - 32 IS - 12 N2 - 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-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. 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). SN - 1745-7254 UR - https://www.unboundmedicine.com/medline/citation/21986574/VEGF_ameliorates_tubulointerstitial_fibrosis_in_unilateral_ureteral_obstruction_mice_via_inhibition_of_epithelial_mesenchymal_transition_ L2 - https://doi.org/10.1038/aps.2011.111 DB - PRIME DP - Unbound Medicine ER -