Reduction in VEGF protein and phosphorylated nephrin associated with proteinuria in adriamycin nephropathy rats.
OBJECTIVE
The relationship between vascular endothelial growth factor (VEGF) and the phosphorylated critical podocyte slit diaphragm molecule nephrin is not fully clarified. This study investigated the dynamic changes in VEGF expression and nephrin phosphorylation, and the effects of the antiproteinuric drugs prednisone and lisinopril on them in Adriamycin nephropathy rats.


METHODS
Renal tissues from Adriamycin rats were collected at days 3, 7, 14, and 28. Distribution and expression of VEGF was revealed by immunohistochemistry, real-time PCR and Western blot. Phosphorylated nephrin was evaluated by immunoprecipitation.


RESULTS
A discontinuous redistribution of VEGF was displayed at day 3, followed by significant protein reduction at day 7 with persistent downregulation to day 28. Phosphorylated nephrin decreased evidently at day 14 and persisted to day 28. The reduction in VEGF and phosphorylated nephrin was not a result of podocyte loss. The intervention of prednisone and lisinopril evidently reduced proteinuria, effectively attenuated the severe lesions of podocyte foot processes, and restored the reduction in VEGF and nephrin phosphorylation. At day 28, the reduction in VEGF and phosphorylated nephrin was negatively correlated with proteinuria, whereas the phosphorylated nephrin was positively correlated with VEGF protein from day 7 to day 28.


CONCLUSIONS
The reduction in VEGF protein and nephrin phosphorylation was possibly involved in the proteinuria in Adriamycin rats, and there might be some relationship between VEGF and nephrin phosphorylation. The antiproteinuric effects of lisinopril and prednisone were achieved at least partially by restoring VEGF protein and nephrin phosphorylation.
Fan
Qingfeng
Q
Department of Pediatrics, Peking University First Hospital, Beijing, PR China.
Xing
Yan
Y
Ding
Jie
J
Guan
Na
N
D000818:Animals; D004317:Doxorubicin / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011507:Proteinuria / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D008565:Membrane Proteins; D042461:Vascular Endothelial Growth Factor A; C113267:nephrin; D004317:Doxorubicin