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

  • Jan Domin
    ,
  • Jacques Behmoaras
    ,
  • Gurjeet Bhangal
    ,
  • Jennifer Smith
    ,
  • Kylie McDonald
    ,
  • Brenda Mutch
  • Imperial College Healthcare NHS Trust
    ,
  • Imperial College London
    ,
  • Chang Gung University
Research Output: Contribution to journal Article Peer-review

Sustainable Development Goals

  • SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well

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.

Publication Information

Output type

Research Output: Contribution to journal Article Peer-review

Original language

English

Pages from-to (Number of pages)

Pages 553-559

Journal (Volume, Issue Number)

Nature Genetics (Volume 40, Issue 5)

Publication milestones

  • Published - 01/05/2008

Publication status

Published - 01/05/2008

ISSN

1061-4036

External Publication IDs

  • handle.net: 10547/228930
  • Scopus: 42649106487

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