The Accumulation of VEGFA in the Glomerular Basement Membrane and Its Relationship with Podocyte Injury and Proteinuria in Alport Syndrome.
The pathogenesis of proteinuria in Alport syndrome (AS) remains unclear. Vascular endothelial growth factor A (VEGFA) is a key regulator of the glomerular filtration barrier (GFB). This study explored the expression of VEGFA in the glomeruli and its accumulation in the glomerular basement membrane (GBM) and their relationship with podocyte injury and proteinuria in Alport syndrome (AS). Clinical data and renal tissues of control patients (11 cases) and AS patients (25 cases) were included. AS patients were further divided into 2 groups according to the quantities of their urinary protein: mild to moderate proteinuria group (proteinuria <50 mg/kg/d, 15 cases) and heavy proteinuria group (proteinuria ≥50 mg/kg/d, 10 cases). The expression and distribution of VEGFA and VEGF receptor 2 (VEGFR2) in the GFB, the phosphorylation of VEGFR2 (p-VEGFR2) and nephrin (p-nephrin), and the expression of synaptopodin and nephrin in the glomeruli were detected by immune electron microscopy and/or immunofluorescence, and their relationships to proteinuria in AS patients were analyzed. The accumulation of VEGFA in the GBM was increased in AS patients. The expression of VEGFA and the levels of p-VEGFR2 and p-nephrin in glomeruli were increased and were positively correlated with the degree of proteinuria in AS patients. The expression of synaptopodin and nephrin were decreased and were negatively correlated with the degree of proteinuria in AS patients. The over expressed VEGFA in the glomeruli and its accumulation in the GBM may activate the VEGFA-VEGFR2 and nephrin signaling pathways and lead to podocyte injury and occurrence of proteinuria in AS.
Children's Kidney Disease Center, Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China; Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, P. R. China.
Haiyan
H
Wang
Children's Kidney Disease Center, Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China.
Zhihui
Z
Yue
Department of Electron Microscopy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, P. R. China.
Jinlang
J
Wu
Children's Kidney Disease Center, Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China.
Ting
T
Liu
Children's Kidney Disease Center, Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China.
Ying
Y
Mo
Children's Kidney Disease Center, Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China.
Xiaoyun
X
Jiang
Children's Kidney Disease Center, Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China.
Liangzhong
L
Sun
D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D050533:Glomerular Basement Membrane / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D009394:Nephritis, Hereditary / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D010766:Phosphorylation; D050199:Podocytes / Q000378:metabolism / Q000473:pathology*; D011507:Proteinuria / Q000209:etiology / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D015415:Biomarkers; D008565:Membrane Proteins; D008840:Microfilament Proteins; C503967:SYNPO protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C113267:nephrin; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2