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[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]

[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]

Chun-Mei He, Fa-Lei Zheng, Yao-Guo Lian, Yan-Ping Liu

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2008 Dec;30(6):703-10.

PMID: 19180920

Abstract:

Objective:
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.
Methods:
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.
Results:
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.
Conclusions:
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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413047	Activin Receptor-Like Kinase 1/Fc Chimera human			Price

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