| c-mip impairs podocyte proximal signaling and induces heavy proteinuria. | |
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MedLine Citation:
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PMID: 20484117 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Idiopathic nephrotic syndrome comprises several podocyte diseases of unknown origin that affect the glomerular podocyte, which controls the permeability of the filtration barrier in the kidney to proteins. It is characterized by the daily loss of more than 3 g of protein in urine and the lack of inflammatory lesions or cell infiltration. We found that the abundance of c-mip (c-maf inducing protein) was increased in the podocytes of patients with various acquired idiopathic nephrotic syndromes in which the podocyte is the main target of injury. Mice engineered to have excessive c-mip in podocytes developed proteinuria without morphological alterations, inflammatory lesions, or cell infiltration. Excessive c-mip blocked podocyte signaling by preventing the interaction of the slit diaphragm transmembrane protein nephrin with the tyrosine kinase Fyn, thereby decreasing phosphorylation of nephrin in vitro and in vivo. Moreover, c-mip inhibited interactions between Fyn and the cytoskeletal regulator N-WASP (neural Wiskott-Aldrich syndrome protein) and between the adaptor protein Nck and nephrin, potentially accounting for cytoskeletal disorganization and the effacement of foot processes seen in idiopathic nephrotic syndromes. The intravenous injection of small interfering RNA targeting c-mip prevented lipopolysaccharide-induced proteinuria in mice. Together, these results identify c-mip as a key component in the molecular pathogenesis of acquired podocyte diseases. |
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Authors:
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Shao-Yu Zhang; Maud Kamal; Karine Dahan; André Pawlak; Virginie Ory; Dominique Desvaux; Vincent Audard; Marina Candelier; Fatima BenMohamed; Fatima Ben Mohamed; Marie Matignon; Christo Christov; Xavier Decrouy; Veronique Bernard; Gilles Mangiapan; Philippe Lang; Georges Guellaën; Pierre Ronco; Djillali Sahali |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-18 |
Journal Detail:
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Title: Science signaling Volume: 3 ISSN: 1937-9145 ISO Abbreviation: Sci Signal Publication Date: 2010 |
Date Detail:
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Created Date: 2010-05-20 Completed Date: 2010-08-24 Revised Date: 2010-11-22 |
Medline Journal Info:
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Nlm Unique ID: 101465400 Medline TA: Sci Signal Country: United States |
Other Details:
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Languages: eng Pagination: ra39 Citation Subset: IM |
Affiliation:
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INSERM, UMR 955, Equipe 21, F-94010 Créteil, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carrier Proteins / biosynthesis, genetics, physiology* Humans Membrane Proteins / metabolism Mice Mice, Transgenic Phosphorylation Podocytes / metabolism, physiology* Protein Binding Proteinuria / physiopathology* Proto-Oncogene Proteins c-fyn / metabolism RNA Interference Signal Transduction / physiology* Wiskott-Aldrich Syndrome Protein, Neuronal / metabolism |
| Chemical | |
Reg. No./Substance:
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0/C-mip protein, mouse; 0/Carrier Proteins; 0/Membrane Proteins; 0/Wiskott-Aldrich Syndrome Protein, Neuronal; 0/c-mip protein, human; 0/nephrin; EC 2.7.1.112/FYN protein, human; EC 2.7.10.2/Proto-Oncogene Proteins c-fyn |
| Comments/Corrections | |
Erratum In:
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Sci Signal. 2010;3(123):er7 Note: Mohamed, Fatima Ben [corrected to BenMohamed, Fatima] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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