Mechanisms of proteinuria: vascular permeability factor in congenital nephrotic syndrome of the Finnish type.
Vascular permeability factor (VPF) is the most potent known mediator of vessel wall permeability. In the kidney, it is expressed preferentially in the glomerular visceral epithelial cells. The present study was designed to clarify the proposed role of VPF in diseases with increased glomerular permeability as here exemplified by the congenital nephrotic syndrome of the Finnish type (CNF). For this, we studied the expression levels and the sites of synthesis of VPF and its kinase-insert domain receptor (KDR) in kidneys of patients with CNF using Northern and in situ hybridization techniques and immunohistologic staining with anti-VPF antibody. In addition, we extended the study to include analysis of fetal kidney tissue and cultured glomerular cells of normal and CNF kidneys. In CNF and in normal kidneys VPF was localized in the visceral epithelial aspect of the glomeruli and in the collecting ducts, as also earlier described. A new finding was its localization also in the juxtaglomerular area. The VPF receptor KDR was found in glomeruli in the endothelial cells, but it was not detected in the peritubular capillaries. no consistent differences in the levels of VPF or KDR mRNAs or in their sites of production were seen in CNF and control samples. Also the distribution of VPF antigen in the CNF kidneys and normal kidneys was similar. Thus, we propose that VPF and KDR are not directly involved in the pathogenesis of the proteinuria in CNF.
Department of Bacteriology and Immunology, University of Helsinki, Finland.
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A
Haltia
M L
ML
Solin
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H
Jalanko
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C
Holmberg
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A
Miettinen
H
H
Holthöfer
D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000235:genetics / Q000652:urine*; D005387:Finland; D006801:Humans; D007223:Infant; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008222:Lymphokines / Q000235:genetics / Q000652:urine*; D009404:Nephrotic Syndrome / Q000473:pathology / Q000652:urine*; D011507:Proteinuria; D012333:RNA, Messenger; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000652:urine*; 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; D020794:Receptor Protein-Tyrosine Kinases