Expression of vascular endothelial growth factor and its receptors Flt-1 and KDR/Flk-1 in chronic cyclosporine nephrotoxicity.
BACKGROUND
Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen involved in angiogenesis, wound healing, and inflammation.


METHODS
Rats placed on low salt diet (LSD) or normal salt diet (NSD) were treated with cyclosporine (CsA) or vehicle (VH) and killed at 7 or 28 days. We studied the expression of VEGF and its receptors Flt-1 and KDR/Flk-1 mRNA by Northern and that of VEGF protein by Western blot.


RESULTS
CsA induced VEGF mRNA and protein expressions at 7 and 28 days in LSD rats. At 7 days, CsA up-regulated the expression of Flt-1 and KDR/Flk-1 receptors; however, at 28 days, Flt-1 remained unchanged whereas KDR/Flk-1 expression declined. In NSD rats, in which the lesion did not develop, the expression of VEGF and its receptors remained similar to control.


CONCLUSIONS
What causes VEGF to be up-regulated remains unclear. Further studies are needed to study the role of hypoxia and other cytokines in relation to VEGF in this model.
Shihab
F S
FS
Division of Nephrology, University of Utah School of Medicine, Salt Lake City 84132, USA. fuad.shihab@hsc.utah.edu
Bennett
W M
WM
Yi
H
H
Andoh
T F
TF
D000818:Animals; D002908:Chronic Disease; D016572:Cyclosporine / Q000506:poisoning*; D004039:Diet, Sodium-Restricted; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000506:poisoning*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D007166:Immunosuppressive Agents; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016572:Cyclosporine; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1