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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.

ORGANISM(S): Mus musculus

PROVIDER: GSE32583 | GEO | 2012/08/02

SECONDARY ACCESSION(S): PRJNA154459

REPOSITORIES: GEO

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

Project description: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.

2012-08-01 | E-GEOD-32583 | biostudies-arrayexpress

Expression data from human with lupus nephritis (LN)

Project description: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 transcriptome of microdissected renal biopsies from patients with lupus nephritis (LN) RNA from glomeruli and tubulointerstitial compartments was extracted and processed for hybridization on Affymetrix microarrays.

2012-06-27 | E-GEOD-32591 | biostudies-arrayexpress

Expression data from human with lupus nephritis (LN)

Project description: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 transcriptome of microdissected renal biopsies from patients with lupus nephritis (LN)

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Project description:Genome-wide alternative splice analysis of RNA from lupus and its severe form lupus nephritis We aimed to explore the genome-wide peripheral blood transcriptome of lupus (SLE) and its severe form lupus nephritis (LN) cases compared to healthy subjects (HC) using high density Affymetrix Human Exon1.0.ST arrays. Analysis revealed 15 splice variants that are differentially expressed between SLE/HC and 99 variants between LN/HC (pâ¤0.05,SI>orâ¤0.5,Benjamin Hochberg-False discovery rate correction). Comparison between LN/SLE revealed 7 variants that are differentially expressed with pâ¤0.05,SI>0.5,Benjamin Hochberg-FDR correction. Pathway analysis of differentially spliced genes revealed 11 significant pathways in SLE and 12 in LN (p<0.05). Analysis of peripheral blood transcriptome revealed signature causative genes that are alternatively spliced, signifying their clinical relevance in the pathophysiology of disease. The extent of differential splicing was found to be higher in LN than in SLE, signifying the need for further in-depth research in the same domain. Present study is the first to reveal the significance of alternative variants in susceptibility to SLE and LN. We analyzed blood from 11 female subjects (5 lupus, 3 lupus nephritis and 3 healthy control) using the Affymetrix Human Exon 1.0 ST platform. Array data was processed by Alt Analyze and Genespring software. No techinical replicates were performed. One of the outiler sample (HC2) was excluded from further analysis.

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Kidney tertiary lymphoid structures in Lupus Nephritis develop into large interconnected networks and resembles lymph nodes in gene signature.

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Project description:This SuperSeries is composed of the following subset Series: GSE32583: Expression data from lupus NZB/W, NZM2410, NZW/BXSB mouse kidneys prenephritic and nephritic. GSE32591: Expression data from human with lupus nephritis (LN) Refer to individual Series

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Expression data from macrophages isolated from lupus NZB/W mouse kidneys prenephritic, nephritic or after complete remission.

Project description:Renal infiltration with mononuclear cells is associated with poor prognosis in SLE. A renal macrophage/dendritic cell signature is associated with onset of nephritis in NZB/W mice and immune modulating therapies can reverse this signature and the associated renal damage despite ongoing immune complex deposition. Our findings suggest that mononuclear phagocytes with an aberrant activation profile contribute to tissue damage in lupus nephritis by mediating both local inflammation and excessive tissue remodeling. We used microarrays to analyze the gene expression of renal isolated macrophages at early stage of lupus (young) during lupus nephritis (sick) and after induction of remission (Rem) NZB/W F4/80hi mouse cells were isolated using flow cytometry; RNA from cells (young, sick and after complete remission) was extracted and processed for hybridization on Affymetrix microarrays.

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