Vascular endothelial growth factor is increased during early stage of diabetic nephropathy in type II diabetic rats.
Vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of diabetic nephropathy. We investigated serial changes of VEGF in the kidney and assessed whether glomerular and urinary VEGF levels are related to the severity of diabetic nephropathy. Furthermore, we examined the relationship between urinary VEGF levels and the urinary albumin excretion (UAE) rate in Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats. Glomerular VEGF mRNA expression and protein synthesis were evaluated by the reverse transcription-polymerase chain reaction, immunohistochemical staining and in situ hybridization. Urinary levels of VEGF were determined by enzyme-linked immunosorbent assay. UAE was significantly higher in OLETF rats than in control Long-Evans-Tokushima-Fatty (LETO) rats throughout the study period. Urinary VEGF levels were significantly higher from 25 to 37 weeks, and then gradually reduced until 55 weeks, although the levels were still higher than those in control rats. Urinary VEGF levels also showed a significant positive correlation with UAE (r=0.262, P=0.045) and serum creatinine (r=0.398, P=0.044), and were found to be independently correlated with UAE by Spearman's rank correlation. By immunohistochemical staining and in situ hybridization, VEGF was mainly detected in the podocytes in the glomeruli. Interestingly, a significant increase in VEGF mRNA expression was observed in the early period of diabetic nephropathy, and this was associated with increased urinary VEGF excretion. Thus, the overproduction of VEGF in the diabetic kidney may participate in the pathogenesis of early-stage diabetic nephropathy.
Cha
Dae Ryong
DR
Department of Internal Medicine, College of Medicine, Korea University, Ansan, South Korea.
Kang
Young Sun
YS
Han
Sang Youb
SY
Jee
Yi Hwa
YH
Han
Kum Hyun
KH
Han
Jee Young
JY
Kim
Young Sik
YS
Kim
Nan Hee
NH
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007668:Kidney / Q000378:metabolism*; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis* / Q000235:genetics / Q000652:urine
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A