Podocyte injury and overexpression of vascular endothelial growth factor and transforming growth factor-beta 1 in adriamycin-induced nephropathy in rats

• Published in: Cytokine (Philadelphia, Pa.) Vol. 59; no. 2; pp. 370 - 376
• Main Authors: Yang, Weina, Wang, Junjian, Shi, Lili, Yu, Linhua, Qian, Yihua, Liu, Yong, Wang, Weixi, Cheng, Shaoli
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2012
• Subjects: Animals; blood chemistry; Blotting, Western; Cell Count; cytokines; Doxorubicin; Focal segmental glomerulosclerosis; Glomerular Basement Membrane - metabolism; Glomerular Basement Membrane - pathology; Glomerular Basement Membrane - ultrastructure; Glomerulosclerosis, Focal Segmental - blood; Glomerulosclerosis, Focal Segmental - complications; Glomerulosclerosis, Focal Segmental - pathology; immunohistochemistry; kidney diseases; Kidney Diseases - blood; Kidney Diseases - chemically induced; Kidney Diseases - complications; Kidney Diseases - metabolism; Male; Membrane Proteins - metabolism; Nephrin; Podocytes - metabolism; Podocytes - pathology; Podocytes - ultrastructure; protein content; Proteinuria; Proteinuria - blood; Proteinuria - complications; Proteinuria - pathology; Rats; Rats, Sprague-Dawley; sclerosis; transforming growth factor beta; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-beta 1; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; vascular endothelial growth factors; Western blotting; Nephrin; Focal segmental glomerulosclerosis; Vascular endothelial growth factor; Transforming growth factor-beta 1; Proteinuria
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2012.04.014

► We discuss the podocyte number in ADR-induced nephropathy. ► A reduction in podocyte number results in proteinuria and FSGS. ► We discuss the expression of nephrin, VEGF and TGF-β1 in ADR-induced nephropathy. ► Altered nephrin, VEGF, and TGF-β1 may have a role for the proteinuria and FSGS. The aim of this study is to investigate the expression of nephrin, vascular endothelial growth factor (VEGF), transforming growth factor-beta 1 (TGF-β1), and podocyte number in adriamycin (ADR)-induced nephropathy. A total of 60 male Sprague–Dawley rats were randomly divided into the control group and the ADR nephropathy group. The nephropathy was induced by tail-vein injection of ADR (4mg/kg) twice at a 14-day interval. The expression levels of nephrin, VEGF, and TGF-β1 in glomeruli were assessed by immunohistochemistry and western blotting. The podocyte number was also evaluated after anti-Wilms’ tumor-1 (WT1) immunohistochemical staining. In addition, the urinary protein content, biochemical parameters in serum samples and glomerular sclerosis index (SI) were compared between groups. In the ADR nephropathy group, the expression levels of nephrin was significantly decreased with the fusion of podocyte foot processes at 6weeks after the first ADR injection, which was associated with a marked proteinuria. A decrease in podocyte number and an increase in SI with the overexpression of both VEGF and TGF-β1 were also observed in the glomeruli at 10weeks after the first ADR injection. This was associated with focal segmental glomerulosclerosis (FSGS). The study data suggest that podocyte injury and decreased nephrin, as well as increased VEGF and TGF-β1, may contribute to the development of proteinuria and FSGS in ADR-induced nephropathy in rats.