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    Jund is a determinant of macrophage activation and is associated with glomerulonephritis susceptibility.

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    Authors
    Behmoaras, Jacques
    Bhangal, Gurjeet
    Smith, Jennifer
    McDonald, Kylie
    Mutch, Brenda
    Lai, Ping Chin
    Domin, Jan
    Game, Laurence
    Salama, Alan D.
    Foxwell, Brian M.
    Pusey, Charles D.
    Cook, H. Terence
    Aitman, Timothy J.
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    Affiliation
    Imperial College
    Issue Date
    2008-05
    
    Metadata
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    Abstract
    Crescentic glomerulonephritis is an important cause of human kidney failure for which the underlying molecular basis is largely unknown. In previous studies, we mapped several susceptibility loci, Crgn1-Crgn7, for crescentic glomerulonephritis in the Wistar Kyoto (WKY) rat. Here we show by combined congenic, linkage and microarray studies that the activator protein-1 (AP-1) transcription factor JunD is a major determinant of macrophage activity and is associated with glomerulonephritis susceptibility. Introgression of Crgn2 from the nonsusceptible Lewis strain onto the WKY background leads to significant reductions in crescent formation, macrophage infiltration, Fc receptor-mediated macrophage activation and cytokine production. Haplotype analysis restricted the Crgn2 linkage interval to a 430-kb interval containing Jund, which is markedly overexpressed in WKY macrophages and glomeruli. Jund knockdown in rat and human primary macrophages led to significantly reduced macrophage activity and cytokine secretion, indicating conservation of JunD function in macrophage activation in rats and humans and suggesting in vivo inhibition of Jund as a possible new therapeutic strategy for diseases characterized by inflammation and macrophage activation.
    Citation
    Behmoaras, J. et al (2008) 'Jund is a determinant of macrophage activation and is associated with glomerulonephritis susceptibility', Nature genetics 40 (5):553-559
    Publisher
    Nature Publishing Group
    Journal
    Nature genetics
    URI
    http://hdl.handle.net/10547/228930
    DOI
    10.1038/ng.137
    PubMed ID
    18443593
    Additional Links
    https://www.nature.com/articles/ng.137
    Type
    Article
    Language
    en
    ISSN
    1546-1718
    ae974a485f413a2113503eed53cd6c53
    10.1038/ng.137
    Scopus Count
    Collections
    Cell and Cryobiology Research Group

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