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.