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

2.50
Hdl Handle:
http://hdl.handle.net/10547/228930
Title:
Jund is a determinant of macrophage activation and is associated with glomerulonephritis susceptibility.
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.
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.
Affiliation:
Physiological Genomics and Medicine Group, Medical Research Council Clinical Sciences Centre, Imperial College, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.
Citation:
Jund is a determinant of macrophage activation and is associated with glomerulonephritis susceptibility. 2008, 40 (5):553-559 Nat. Genet.
Publisher:
Nature Publishing Group
Journal:
Nature genetics
Issue Date:
May-2008
URI:
http://hdl.handle.net/10547/228930
DOI:
10.1038/ng.137
PubMed ID:
18443593
Type:
Article
Language:
en
ISSN:
1546-1718
Appears in Collections:
Cell and Cryobiology Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorBehmoaras, Jacquesen_GB
dc.contributor.authorBhangal, Gurjeeten_GB
dc.contributor.authorSmith, Jenniferen_GB
dc.contributor.authorMcDonald, Kylieen_GB
dc.contributor.authorMutch, Brendaen_GB
dc.contributor.authorLai, Ping Chinen_GB
dc.contributor.authorDomin, Janen_GB
dc.contributor.authorGame, Laurenceen_GB
dc.contributor.authorSalama, Alan D.en_GB
dc.contributor.authorFoxwell, Brian M.en_GB
dc.contributor.authorPusey, Charles D.en_GB
dc.contributor.authorCook, H. Terenceen_GB
dc.contributor.authorAitman, Timothy J.en_GB
dc.date.accessioned2012-06-14T11:49:01Z-
dc.date.available2012-06-14T11:49:01Z-
dc.date.issued2008-05-
dc.identifier.citationJund is a determinant of macrophage activation and is associated with glomerulonephritis susceptibility. 2008, 40 (5):553-559 Nat. Genet.en_GB
dc.identifier.issn1546-1718-
dc.identifier.pmid18443593-
dc.identifier.doi10.1038/ng.137-
dc.identifier.urihttp://hdl.handle.net/10547/228930-
dc.description.abstractCrescentic 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.en_GB
dc.language.isoenen
dc.publisherNature Publishing Groupen_GB
dc.rightsArchived with thanks to Nature geneticsen_GB
dc.subject.meshAnimals-
dc.subject.meshAnimals, Congenic-
dc.subject.meshChromosome Mapping-
dc.subject.meshGene Expression-
dc.subject.meshGenetic Linkage-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshGlomerulonephritis-
dc.subject.meshHaplotypes-
dc.subject.meshHumans-
dc.subject.meshMacrophage Activation-
dc.subject.meshProto-Oncogene Proteins c-jun-
dc.subject.meshRats-
dc.subject.meshRats, Inbred Lew-
dc.subject.meshRats, Inbred WKY-
dc.subject.meshTranscription Factor AP-1-
dc.titleJund is a determinant of macrophage activation and is associated with glomerulonephritis susceptibility.en
dc.typeArticleen
dc.contributor.departmentPhysiological Genomics and Medicine Group, Medical Research Council Clinical Sciences Centre, Imperial College, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.en_GB
dc.identifier.journalNature geneticsen_GB

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