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- Title
Induction of B7-1 in podocytes is associated with nephrotic syndrome.
- Authors
Reiser, Jochen; Von Gersdorff, Gero; Loos, Martin; Oh, Jun; Asanuma, Katsuhiko; Giardino, Laura; Rastaldi, Maria Pia; Calvaresi, Novella; Watanabe, Haruko; Schwarz, Karin; Faul, Christian; Kretzler, Matthias; Davidson, Anne; Sugimoto, Hikaru; Kalluri, Raghu; Sharpe, Arlene H.; Kreidberg, Jordan A.; Mundep, Peter
- Abstract
Kidney podocytes and their slit diaphragms form the final barrier to urinary protein loss.This explains why podocyte injury is typically associated with nephrotic syndrome.The present study uncovered an unan- ticipated novel role for costimulatory molecule B7-1 in podocytes as an inducible modifier of glomerular permselectivity.B7-1 in podocytes was found in genetic,drug-induced,immune-mediated,and bacterial toxin--induced experimental kidney diseases with nephrotic syndrome.The clinical signif icance of our results is underscored by the observation that podocyte expression of B7-1 correlated with the severity of human lupus nephritis.In vivo,exposure to low-dose LPS rapidly upregulates B7-1 in podocytes of WT and SCID mice,leading to nephrotic-range proteinuria.Mice lacking B7-1 are protected from LPS-induced nephrotic syndrome,suggesting a link between podocyte B7-1 expression and proteinuria.LPS signaling through toll-like receptor-4 reorganized the podocyte actin cytoskeleton in vitro,and activation of B7-1 in cultured podocytes led to reorganization of vital slit diaphragm proteins.In summary,upregulation of B7-1 in podocytes may contribute to the pathogenesis of proteinuria by disrupting the glomerular filter and pro- vides a novel molecular target to tackle proteinuric kidney diseases.Our findings suggest a novel function for B7-1 in danger signaling by nonimmune cells.
- Subjects
NEPHROTIC syndrome; KIDNEY diseases; PROTEINS; PROTEINURIA; TOXINS; KIDNEY glomerulus
- Publication
Journal of Clinical Investigation, 2004, Vol 113, Issue 10, p1390
- ISSN
0021-9738
- Publication type
Article
- DOI
10.1172/JCI200420402