NEMO is distinct from IKK2 by regulating non-canonical pathway in the experimental nephrotoxic serum nephritis mouse model
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PROVIDER: PRJNA419900 | ENA |
REPOSITORIES: ENA
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Project description:Experimental nephrotoxic serum nephritis (NTN) is a model for T-cell mediated human rapid progressive glomerulonephritis. T-cell receptor (TCR) stimulation leads to intracellular signaling events ultimately causing activation of transcription factors, such as NF-κB. Using CD4creIKK2fl/fl (CD4xIKK2Δ) and CD4creNEMOfl/fl (CD4xNEMOΔ) and CD4cre mice our results demonstrated that NTN was not attenuated in CD4xIKK2Δ, CD4xNEMOΔ when compared with CD4cre mice as showing no significant kidney functional difference with respect to BUN and proteinuria data as well as histological damage. Although the percentage of CD4+ T cells infiltrating kidneys was not significantly changed between the examined groups on day 10, further analysis showed significantly reduced Tregs and significant increase in Th1 and Th17 cells in CD4xIKK2Δ and CD4xNEMOΔ mice. The expression of renal cytokines and chemokines, IL-1β, CCL2 and CCL20, was significantly changed in CD4xIKK2Δ and CD4xNEMOΔ mice when compared with nephritic CD4cre animals. The microarray data confirmed the increased expression of Th17 related cytokines in splenetic CD4+ T cells. More importantly, our array data also demonstrated the interrupted canonical pathway in nephritic CD4xNEMOΔ mice, which highlighted the possible different downstream pathway when IKK2 or NEMO is specifically deleted in lymphocytes. By combining microarray gene expression and bioinformatics analyses our data have identified genes involved in T cell proliferation and differentiation that were differentially expressed between IKK2 and NEMO deficient CD4+ T cells. We propose that better understanding the role of IKK2 and NEMO in T cell regulation will help to recognize the role of IKK2 and NEMO kinase inhibitors in the clinical application in patients with glomerulonephritis.
2018-11-30 | GSE107364 | GEO
Project description:We induced acute nephritis by single injection of sheep nephrotoxic serum in mice and then treated the mice with prostaglandin E2. We used microarrays to examine the global gene expressions during recovery from nephrotoxic nephritis by prostaglandin E2.
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Project description:We induced acute nephritis by single injection of sheep nephrotoxic serum in mice and then treated the mice with prostaglandin E2. We used microarrays to examine the global gene expressions during recovery from nephrotoxic nephritis by prostaglandin E2. Acute nephristis was induced in female mice by single injection of sheep Nephortoxc Serum (NTS), followed by prostaglandin E2 administration daily starting from day 2 after NTS administration. Mice were sacrificed on day 7 and RNAs were isolated from kidney. The RNA samples were subjected to mouse gene 1.0 ST array analysis.
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Project description:The goal of our study was to characterize glomerulus and particularly podocyte biology during MMF treatment in an immune-triggered proteinuric glomerulopathy. Therefore, nephrotoxic serum nephritis was induced in three-week old wild-type mice. On day 3, half of the mice were treated with MMF (100 mg/kgBW/d p.o.) (NTS+MMF) for one week, the other half of animals with vehicle (NTS+veh). A further group without induction and treatment served as controls (C). On day 10, we performed proteomic analysis of glomeruli.
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2008-04-01 | E-MEXP-1294 | biostudies-arrayexpress
Project description:Studying the differences in glycosylation in B cells of normal mice and mice with an autoimmune disease (nephrotoxic nephritis). Differences in glycosylation in B cells of normal mice and mice with an autoimmune disease (nephrotoxic nephritis) were studied via gene expression analysis. RNA from mouse resting spleen B cells and B cells stimulated with antiCD40, CpG, and IL4 for 5 days, was isolated and prepared. One sample for each class was prepared. RNA was labeled and hybridized to the GLYCOv3 array. Resulting Gene expression patterns were analyzed.
2011-06-14 | E-GEOD-29923 | biostudies-arrayexpress
Project description:Studying the differences in glycosylation in B cells of normal mice and mice with an autoimmune disease (nephrotoxic nephritis).
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Project description:One single-cell RNA transcriptomic dataset was originated from one wild-type mouse, which was harvested at 3 months after nephrotoxic nephritis model.
2023-08-28 | GSE241314 | GEO
Project description:Classical dendritic cells (DCs) are key players at the interface between innate and adaptive immunity. In the kidney exist 2 major subsets of cDCs: CD11b+ cDCs and CD103+ cDCs. We investigated their function in the most widely used model of experimental glomerulonephritis (GN) in mice: nephrotoxic nephritis (NTN). Consistent with a role for cDCs in nephrotoxic nephritis, depletion of ZBTB46+ cells (all cDCs) attenuated kidney injury, while deficiency of the CD103+ subset of cDCs accelerated injury via a mechanism that involved increased neutrophils. This RNAseq was performed to analyze transcriptional changes in FACS-sorted renal CD11b+ and CD103+ cDCs under healthy conditions and at day 7 of NTN to reveal why both subsets have different functions in GN.
2017-10-12 | GSE104820 | GEO
Project description:Signal transduction by the NF-kappaB pathway is a key regulator of a host of cellular responses to extracellular and intracellular messages. The NEMO adaptor protein lies at the top of this pathway and serves as a molecular conduit, connecting signals transmitted from upstream sensors to the downstream NF-kappaB transcription factor and subsequent gene activation. The position of NEMO within this pathway makes it an attractive target from which to search for new proteins that link NF-kappaB signaling to additional pathways and upstream effectors. In this work, we have used protein microarrays to identify novel NEMO interactors. A total of 112 protein interactors were identified, with the most statistically significant hit being the canonical NEMO interactor IKKbeta, with IKKalpha also being identified. Of the novel interactors, more than 30% were kinases, while at least 25% were involved in signal transduction. Binding of NEMO to several interactors, including CALB1, CDK2, SAG, SENP2 and SYT1, was confirmed using GST pulldown assays and coimmunoprecipitation, validating the initial screening approach. Overexpression of CALB1, CDK2 and SAG was found to stimulate transcriptional activation by NF-kappaB, while SYT1 overexpression repressed TNFalpha-dependent NF-kappaB transcriptional activation in human embryonic kidney cells. Corresponding with this finding, RNA silencing of CDK2, SAG and SENP2 reduced NF-kappaB transcriptional activation, supporting a positive role for these proteins in the NF-kappaB pathway. The identification of a host of new NEMO interactors opens up new research opportunities to improve understanding of this essential cell signaling pathway. For microarray screening, Invitrogen Protoarray v4.0 protein microarrays were used. Human NEMO expressed as a C-terminal GST fusion was purified from E. coli lysates and labelled with biotin. NEMO or biotinylated GST were applied to the microarrays and binding partners detected using streptavidin-Alexa Fluor 647. Significant interactors on both arrays were detected using Invitrogen Protoarray Prospector software and a Z-score cutoff of 3.0. Following subtraction of interactors present on the GST control array, a final set of significant NEMO interactors was derived. Full experimental details are supplied in Fenner, B. J., Scannell, M. & Prehn, J. H. M. (2010). Expanding the substantial interactome of NEMO using protein microarrays. PLoS ONE (in press).
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