title: 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.
authors.affiliation: Department of Nephrology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Xiangchun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Kezhou
authors.initials: K
authors.lastname: Yu
authors.affiliation: Department of Nephrology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D010766:Phosphorylation; D050199:Podocytes / Q000187:drug effects / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D011758:Pyrroles / Q000494:pharmacology*; D015533:Transcriptional Activation; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D007211:Indoles; D008840:Microfilament Proteins; D011758:Pyrroles; C503968:Synpo protein, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D000804:Angiotensin II; C116890:Semaxinib; C000592875:Kdr protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D048049:Extracellular Signal-Regulated MAP Kinases