Nephrology Dialysis Transplantation, Vol 13, Issue 10 2519-2528, Copyright © 1998 by Oxford University Press
Y Horita, M Miyazaki, T Koji, N Kobayashi, M Shibuya, M Razzaque, M Cheng, Y Ozono, S Kohno and T Taguchi
Background. Based on the fact that vascular
endothelial growth factor (VEGF) increases vascular permeability, it is
speculated that VEGF might be involved in the development of proteinuria,
although this remains unconfirmed. The production and site of action of
VEGF remains unclear in nephrotic renal diseases. Methods.
Non-radioactive in situ hybridization was
performed to examine the expression of VEGF mRNA and its receptors, flt-1
and KDR/flk-1, in a rat model of nephrosis induced by intraperitoneal
injection of bovine serum albumin (BSA). Saline injected rats were served
as control animals. Results. Neither morphological
changes nor deposition of immunoglobulin or complement were observed in our
model. Proteinuria developed, reaching a maximum level in rats injected
with BSA for 3 days, followed by persistent proteinuria until day 14. The
expression of mRNA for VEGF and the two receptors was markedly upregulated
in glomeruli of BSA-induced nephritis compared with the control group. VEGF
mRNA was localized in glomerular cells, including cells in mesangium,
visceral and parietal epithelial cells. In contrast, flt-1 mRNA and
KDR/flk-1 mRNA were expressed on glomerular endothelial cells and cells in
mesangium. The ratio of glomerular cells positive for VEGF mRNA and its
receptors mRNA increased proportionately with the severity of proteinuria.
Immunohistochemistry for ED-1 and proliferating cell nuclear antigen showed
no significant increase in infiltrating macrophage or cellular
proliferation. Conclusions. Our results suggest that
altered glomerular expression of VEGF and its receptors is not associated
with proliferation of endothelial cells, but rather with proteinuria in
BSA-induced nephritis in rats, VEGF may play a different role in different
renal diseases. Keywords: VEGF; flt-1; KDR/flk-1,
proteinuria; in situ hybridization; rats
ORIGINAL ARTICLES
Expression of vascular endothelial growth factor and its receptors in rats with protein-overload nephrosis
Second Department of Pathology, Second Department of Internal Medicine, Third Department of Anatomy, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki 852-8501, Japan; Department of Clinical Pharmaceutics, Nagasaki University School of Pharmaceutical Sciences, Nagasaki, Japan; Department of Genetics, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Corresponding author
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