title: Podocyte injury and overexpression of vascular endothelial growth factor and transforming growth factor-beta 1 in adriamycin-induced nephropathy in rats.
abstract: 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 (4 mg/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 6 weeks 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 10 weeks 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.
authors.affiliation: Department of Anatomy, Histology & Embryology, Medicine School of Xi'an Jiaotong University, Xi'an, PR China.
authors.forename: Weina
authors.initials: W
authors.lastname: Yang
authors.forename: Junjian
authors.initials: J
authors.lastname: Wang
authors.forename: Lili
authors.initials: L
authors.lastname: Shi
authors.forename: Linhua
authors.initials: L
authors.lastname: Yu
authors.forename: Yihua
authors.initials: Y
authors.lastname: Qian
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Weixi
authors.initials: W
authors.lastname: Wang
authors.forename: Shaoli
authors.initials: S
authors.lastname: Cheng
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D004317:Doxorubicin; D050533:Glomerular Basement Membrane / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D005923:Glomerulosclerosis, Focal Segmental / Q000097:blood / Q000150:complications / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000150:complications / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D011507:Proteinuria / Q000097:blood / Q000150:complications / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C113267:nephrin; D004317:Doxorubicin