Jund is a determinant of macrophage activation and is associated with glomerulonephritis susceptibility.
Authors
Behmoaras, JacquesBhangal, 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.
Affiliation
Imperial CollegeIssue Date
2008-05
Metadata
Show full item recordAbstract
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):553-559Publisher
Nature Publishing GroupJournal
Nature geneticsDOI
10.1038/ng.137PubMed ID
18443593Additional Links
https://www.nature.com/articles/ng.137Type
ArticleLanguage
enISSN
1546-1718ae974a485f413a2113503eed53cd6c53
10.1038/ng.137
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