| Induction of B7-1 in podocytes is associated with nephrotic syndrome. | |
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MedLine Citation:
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PMID: 15146236 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 unanticipated 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 significance 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 provides a novel molecular target to tackle proteinuric kidney diseases. Our findings suggest a novel function for B7-1 in danger signaling by nonimmune cells. |
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Authors:
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Jochen Reiser; Gero von Gersdorff; Martin Loos; Jun Oh; Katsuhiko Asanuma; Laura Giardino; Maria Pia Rastaldi; Novella Calvaresi; Haruko Watanabe; Karin Schwarz; Christian Faul; Matthias Kretzler; Anne Davidson; Hikaru Sugimoto; Raghu Kalluri; Arlene H Sharpe; Jordan A Kreidberg; Peter Mundel |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 113 ISSN: 0021-9738 ISO Abbreviation: J. Clin. Invest. Publication Date: 2004 May |
Date Detail:
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Created Date: 2004-05-17 Completed Date: 2004-06-17 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States |
Other Details:
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Languages: eng Pagination: 1390-7 Citation Subset: AIM; IM |
Affiliation:
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Department of Medicine, Albert Einstein College of Medicine, New York, New York 10461, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Actins
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metabolism Animals Antigens, CD80 / biosynthesis*, genetics Base Sequence DNA / genetics Humans Integrin alpha3 / genetics, metabolism Kidney / immunology*, pathology Lipopolysaccharides / toxicity Lupus Nephritis / etiology, immunology, pathology Membrane Glycoproteins / metabolism Membrane Proteins Mice Mice, Knockout Mice, SCID Nephrotic Syndrome / etiology, immunology*, pathology Proteins / genetics, metabolism Receptors, Cell Surface / metabolism Signal Transduction Toll-Like Receptor 4 Toll-Like Receptors |
| Grant Support | |
ID/Acronym/Agency:
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DK062472/DK/NIDDK NIH HHS; DK064236/DK/NIDDK NIH HHS; DK55001/DK/NIDDK NIH HHS; DK57683/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/Antigens, CD80; 0/Integrin alpha3; 0/Lipopolysaccharides; 0/Membrane Glycoproteins; 0/Membrane Proteins; 0/Proteins; 0/Receptors, Cell Surface; 0/TLR4 protein, human; 0/Toll-Like Receptor 4; 0/Toll-Like Receptors; 0/nephrin; 9007-49-2/DNA |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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