Blockade of vascular endothelial growth factor-A/receptor 2 exhibits a protective effect on angiotensin-II stimulated podocytes.

Abstract:

:Vascular endothelial growth factor (VEGF) and Angiotensin II (Ang-II) are important in glomerulosclerosis, which is one of the main causes of chronic kidney disease. Previous studies have demonstrated that angiotensin type 1 receptor blocker (ARB) can inhibit the synthesis of VEGF mediated by Ang‑II and can effectively treat diabetic nephropathy. In the present study, the expression of VEGF and its receptors (VEGFR1/VEGFR2) was examined in Ang‑II stimulated podocytes, which were treated with SU5416, a specific VEGFR2 inhibitor. The protein expression of synaptopodin, VEGFR1/2, phosphorylated VEGFR2 and extracellular signal‑regulated kinases (ERK) was assessed by western blot analysis. The mRNA expression of transforming growth factor (TGF)‑β1 was examined by reverse transcription‑quantitative polymerase chain reaction. It was observed that Ang‑II increased the expression of VEGF‑A and VEGFR2. Simultaneously, the increased expression of phosphorylated (p‑)VEGFR2 and p‑ERK induced by Ang‑II was downregulated by SU5416. SU5416 can decrease the expression of synaptopodin and increase the expression of TGF‑β1 induced by Ang‑II as well as ARB treatment. The expression of VEGFR1 remained unchanged by either Ang‑II or SU5416 treatment. However, the normal podocytes administered SU5416 alone showed low levels of synaptopodin and high expression of TGF‑β1 compared with the control. In conclusion, VEGF‑A/VEGFR2 may be essential for podocytes in a normal state. It is suggested that blockade of VEGF‑A/VEGFR2 may exhibit a protective effect on Ang-II stimulated podocytes.

journal_name

Mol Med Rep

authors

Liu X,Zhang H,Wang Q,Yu K,Wang R,Sun J

doi

10.3892/mmr.2015.3911

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

4340-4345

issue

3

eissn

1791-2997

issn

1791-3004

journal_volume

12

pub_type

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