Transcriptomics

Dataset Information

21

Expression data from lupus NZB/W, NZM2410, NZW/BXSB mouse kidneys prenephritic and nephritic.


ABSTRACT: Nephritis (LN) is a serious manifestation of SLE. Therapeutic studies in mouse LN models do not always predict outcomes of human therapeutic trials, raising concerns about the human relevance of these models. In this study we used an unbiased transcriptional network approach to define similarities and differences between three lupus models and human LN. Affymetrix-based expression profiles were analyzed using Genomatix Bibliosphere software and transcriptional networks were compared using the Tool for Approximate LargE graph matching (TALE). The 20 network hubs (nodes) shared between all three models and human LN reflect key pathologic processes, namely immune cell infiltration/activation, macrophage/dendritic cell activation, endothelial cell activation/injury and tissue remodeling/fibrosis. Each model also shares unique features with human LN. Pathway analysis of the TALE nodes highlighted macrophage/DC activation as a cross-species shared feature. To distinguish which genes and activation pathways might derive from mononuclear phagocytes in the human kidneys the gene expression profile of isolated NZB/W renal mononuclear cells was compared with human LN kidney profiles. Network analysis of the shared signature highlighted NFkappaB1 and PPARgamma as major hubs in the tubulointerstitial and glomerular networks respectively. Key nodes in the renal macrophage inflammatory response form the basis for further mechanistic and therapeutic studies. We used microarrays to analyze the renal transcriptome of three different lupus mouse models, at early stage of lupus and during lupus nephritis. RNA from whole kidneys was extracted and processed for hybridization on Affymetrix microarrays.

ORGANISM(S): Mus musculus  

SUBMITTER: Celine C Berthier   Erwin P Bottinger  Weija Zhang  Matthias Kretzler  Stephan Segerer  Meera Ramanujam  Viji Nair  Tania Gonzalez-Rivera  Anne Davidson  Ramalingam Bethunaickan 

PROVIDER: E-GEOD-32583 | ArrayExpress | 2012-08-01

SECONDARY ACCESSION(S): GSE32583PRJNA154459

REPOSITORIES: GEO, ArrayExpress

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Publications

Cross-species transcriptional network analysis defines shared inflammatory responses in murine and human lupus nephritis.

Berthier Celine C CC   Bethunaickan Ramalingam R   Gonzalez-Rivera Tania T   Nair Viji V   Ramanujam Meera M   Zhang Weijia W   Bottinger Erwin P EP   Segerer Stephan S   Lindenmeyer Maja M   Cohen Clemens D CD   Davidson Anne A   Kretzler Matthias M  

Journal of immunology (Baltimore, Md. : 1950) 20120620 2


Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus. Therapeutic studies in mouse LN models do not always predict outcomes of human therapeutic trials, raising concerns about the human relevance of these preclinical models. In this study, we used an unbiased transcriptional network approach to define, in molecular terms, similarities and differences among three lupus models and human LN. Genome-wide gene-expression networks were generated using natural language proces  ...[more]

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