Role of vascular endothelial growth factor in diabetic nephropathy.
BACKGROUND
Vascular endothelial growth factor (VEGF) is a potent cytokine that is considered to be an important mediator in the pathogenesis of endothelial dysfunction in diabetes.


METHODS
This study investigates the effect of high glucose on the signaling and production of VEGF in rat mesangial cells in culture and measures the urinary VEGF level in patients with different stages of diabetic nephropathy. To elucidate the role of VEGF in vivo further, expression of VEGF in control and diabetic kidneys was examined using immunohistochemistry.


RESULTS
A high ambient glucose concentration in the culture medium increased VEGF mRNA expression and protein production within 3 h in a concentration-dependent manner. A protein kinase C (PKC) inhibitor and PKC down-regulation inhibited glucose-induced increases in VEGF production. Urinary excretion of VEGF significantly increased according to the degree of proteinuria in patients with diabetes. A weak but significant correlation was found between urinary VEGF excretion and the levels of serum creatinine, creatinine clearance, microalbuminuria, and proteinuria. Immunohistochemistry revealed marked differences in the extent of mesangial VEGF staining between diabetic and control kidneys. Pronounced up-regulation of VEGF was observed in the glomerular epithelial cell in the early phase of diabetic kidney disease, whereas widespread expression of VEGF was found in the tubular segments, especially the proximal segment, in advanced diabetic nephropathy.


CONCLUSIONS
These results suggest that VEGF may play a role in the pathogenesis of diabetic nephropathy.
Cha
D R
DR
Department of Internal Medicine and Pathology, College of Medicine, Korea University, Institute of Renal Disease, Ansan City, Kyungki-Do. cdragn@unitel.co.kr
Kim
N H
NH
Yoon
J W
JW
Jo
S K
SK
Cho
W Y
WY
Kim
H K
HK
Won
N H
NH
D000818:Animals; D015153:Blotting, Western; D003928:Diabetic Nephropathies / Q000209:etiology*; D016228:Endothelial Growth Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry; D008222:Lymphokines / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D008297:Male; D011493:Protein Kinase C / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D011493:Protein Kinase C; D005947:Glucose