title: Expression of vascular endothelial growth factor and its receptors in rats with protein-overload nephrosis.
abstract: 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.
authors.affiliation: Second Department of Pathology, Nagasaki University School of Medicine, Sakamoto, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Horita
authors.forename: M
authors.initials: M
authors.lastname: Miyazaki
authors.forename: T
authors.initials: T
authors.lastname: Koji
authors.forename: N
authors.initials: N
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Shibuya
authors.forename: M S
authors.initials: MS
authors.lastname: Razzaque
authors.forename: M
authors.initials: M
authors.lastname: Cheng
authors.forename: Y
authors.initials: Y
authors.lastname: Ozono
authors.forename: S
authors.initials: S
authors.lastname: Kohno
authors.forename: T
authors.initials: T
authors.lastname: Taguchi
mesh_terms: D000818:Animals; D002455:Cell Division; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D009401:Nephrosis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D011507:Proteinuria / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; 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
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1