title: Downregulation of vascular endothelial growth factor and its receptors in the kidney in rats with puromycin aminonucleoside nephrosis.
abstract: OBJECTIVE
  We aimed to examine the possible involvement of vascular endothelial growth factor (VEGF) in the pathogenesis of puromycin aminonucleoside nephrosis (PAN).
  
  
  METHODS
  The expression and localization of the mRNA of VEGF and its receptors, flt-1 and flk-1, were analyzed in the kidneys of puromycin aminonucleoside-injected rats by use of Northern blotting and in situ hybridization.
  
  
  RESULTS
  In association with the induction of proteinuria, VEGF mRNA underwent decrease in amount from 3 days after the injection, reaching the minimum level at 7 days, followed by a gradual recovery by 28 days. The levels of flk-1 and flt-1 mRNA showed similar transient decrease in PAN kidney, whereas the mRNA of von Willebrand factor, a marker of endothelial cells, showed no change in amount. In the normal rat kidney, VEGF mRNA was localized primarily to podocytes, and flk-1 mRNA was localized exclusively to endothelial cells with much higher intensity in glomeruli than in peritubular capillaries. In PAN kidney, the intensities of both VEGF and flk-1 signals in podocytes and glomerular endothelial cells, respectively, appeared much lower at 7 days than in normal kidney.
  
  
  CONCLUSIONS
  These results indicate that the VEGF-VEGF receptor system is downregulated in PAN, implying that it is not involved in the mechanism of proteinuria in PAN.
authors.affiliation: Department of Anatomy, School of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Liying
authors.initials: L
authors.lastname: Fan
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Wakayama
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Osamu
authors.initials: O
authors.lastname: Amano
authors.forename: Shoichi
authors.initials: S
authors.lastname: Iseki
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D004195:Disease Models, Animal; D015536:Down-Regulation; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D007668:Kidney / Q000166:cytology / Q000503:physiopathology*; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009402:Nephrosis, Lipoid / Q000139:chemically induced / Q000378:metabolism*; D011507:Proteinuria / Q000139:chemically induced; D011692:Puromycin Aminonucleoside; 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; D042442:Vascular Endothelial Growth Factors
chemical_list: D000903:Antibiotics, Antineoplastic; D016228:Endothelial Growth Factors; D008222:Lymphokines; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D011692:Puromycin Aminonucleoside; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor