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GSE8611
Homo sapiens
11 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Multipotent progenitor cells (MPs) have been observed in human kidneys and particularly in Bowman's capsule and proximal tubules. The kidney owns the ability to repair local damage and renal MPs may play a role in the regenerative processes. Microarray technology was applied to identify differentially expressed genes among resident MPs isolated from glomeruli and tubules of normal renal tissue, renal proximal tubular epithelial cells (RPTECs) and mesenchymal stem cells (MSCs).
Publication Title
TLR2 plays a role in the activation of human resident renal stem/progenitor cells.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Several reports have focused on the identification of biological elements involved in the development of abnormal systemic biochemical alterations in chronic kidney disease, but this abundant literature results most of the time fragmented. To better define the cellular machinery associated to this condition, we employed an innovative high-throughput approach based on a whole transcriptomic analysis and classical biomolecular methodologies. The genomic screening of peripheral blood mononuclear cells revealed that 44 genes were up-regulated in both chronic kidney disease patients in conservative treatment (CKD, n=9) and hemodialysis (HD, n=17) compared to healthy subjects (NORM) (p<0.001, FDR=1%). Functional analysis demonstrated that 11/44 genes were involved in the oxidative phosphorylation system (OXPHOS). Western blotting for COXI and COXIV, key constituents of the complex IV of OXPHOS, performed on an independent testing-group (12 NORM, 10 CKD and 14 HD) confirmed the elevated synthesis of these subunits in CKD/HD patients. However, complex IV activity was significantly reduced in CKD/HD patients compared to NORM (p<0.01). Finally, CKD/HD patients presented higher reactive oxygen species and 8-hydroxydeoxyguanosine levels compared to NORM. Taken together these results suggest, for the first time, that CKD/HD patients may have an impaired mitochondrial respiratory system and this condition may be both the consequence and the cause of an enhanced oxidative stress.
Publication Title
Mitochondrial dysregulation and oxidative stress in patients with chronic kidney disease.
Sample Metadata Fields
Disease, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The hallmark of IgA nephropathy (IgAN) is gross hematuria (GH) coinciding with or immediately following an upper respiratory or gastrointestinal tract infection and can represent the disease triggering event. Therefore, a whole genomic screening of IgAN patients during the GH was done to clarify the link between mucosal encountered antigens and the occurrence of glomerular hematuria. The modulated genes during GH show a clear involvement of the interferon signalling, antigen presenting pathway, and the immuno-proteasome. The gene characterizing cytotoxic effector lymphocytes (CX3CR1) implicated in vascular endothelial damage, was found up-regulated at both mRNA and protein level. In vitro antigenic stimulation of PBMCs on an independent set of IgAN patients and healthy blood donors (HBS) demonstrated that patients upregulate specifically CX3CR1 in an enhanced and dose dependant manner, while an expected down-regulation occurred in HBD. This enhanced activation occurred in both patients characterized by recurrent GH and by permanent microscopic hematuria (MH). We then analyzed glomerular fractalkine (FKN) expression, since this ligand is involved in the vascular gateway for CX3CR1+ cells towards the inflamed tissues. A significantly higher FKN expression on the capillary vessels and podocytes was found in recurrent GH patients compared to permanent MH, suggesting a predisposition for cytotoxic cell extravasation in recurrent GH patients.
Publication Title
Activated innate immunity and the involvement of CX3CR1-fractalkine in promoting hematuria in patients with IgA nephropathy.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
To uncover new molecular mechanisms involved in IgAN pathogenesis, we compared the genomic profiles of 12 IgAN patients with 8 healthy subjects,
Publication Title
Altered modulation of WNT-beta-catenin and PI3K/Akt pathways in IgA nephropathy.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Mycophenolic acid (MPA), an immunosuppressive drug widely used in kidney transplantation, has been suggested to have anti-fibrotic effects.
Publication Title
The anti-fibrotic effect of mycophenolic acid-induced neutral endopeptidase.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
CD14 regulates the dendritic cell life cycle after LPS exposure through NFAT activation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
BACKGROUND: Mammalian microRNAs (miR) regulate the expression of genes relevant for the development of adaptive and innate immunity against cancer. Since T cell dysfunction has previously been reported in patients with renal cell carcinoma (RCC; clear cell type), we aimed to analyse these immune cells for genetic and protein differences when compared to normal donor T cells freshly after isolation and 35 days after in vitro stimulation (IVS) with HLA-matched RCC tumor cells.
Publication Title
miR-29b and miR-198 overexpression in CD8+ T cells of renal cell carcinoma patients down-modulates JAK3 and MCL-1 leading to immune dysfunction.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Subject, Time
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Interleukin-2 (IL-2) is one of the molecules produced by mouse dendritic cells (DCs) after stimulation by Toll like receptor (TLR) agonists. By analogy with the events following T-cell receptor (TCR) engagement leading to IL-2 production we have observed that DC stimulation with lipopolysaccharide (LPS) induces Src-family kinase and phospholipase C (PLC)2 activation, influx of extracellular Ca2+ and calcineurin-dependent nuclear NFAT translocation. We have also observed that the initiation of this pathway is independent of TLR4 engagement, and dependent exclusively on CD14. To determine the role of NFAT in LPS activated dendritic cells we have performed microarray analysis in conditions allowing or inhibiting NFAT activation. We show here that LPS-induced NFAT activation via CD14 is necessary to cause death of terminally differentiated DCs, an event that is essential for maintaining self-tolerance and preventing autoimmunity. Consequently, blocking this pathway in vivo causes prolonged DC survival and an increase in T cell priming capability.
Publication Title
CD14 regulates the dendritic cell life cycle after LPS exposure through NFAT activation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Dendritic cells (DCs) are a special class of leukocytes able to activate both innate and adaptive immune responses. They interact with microbes through germline-encoded pattern-recognition receptors (PRRs), which recognize molecular patterns expressed by various microorganisms. Upon antigen binding, PRRs instruct DCs for the appropriate priming of natural killer cells, followed by specific T-cell responses. Once completed the effector phase, DCs reach the terminal differentiation stage and eventually die by apoptosis. We have observed that following lipopolysaccharide (LPS)-stimulation the initiation of the apoptotic pathway in DCs is due the activation of NFAT proteins. Indeed, LPS induces Src-family kinase and phospholipase C (PLC)2 activation, influx of extracellular Ca2+ and calcineurin-dependent nuclear NFAT translocation. The initiation of this pathway is independent of TLR4 engagement, and dependent exclusively on CD14. According with this observation CD14-deficient DCs do not die following LPS stimulation. Nevertheless, CD14-deficient DC death following LPS activation can be restored by co-stimulating DCs with LPS and thapsigargin. Thapsigargin empties the intracellular calcium stores by blocking calcium pumping into the sarcoplasmic and endoplasmic reticulum and thereby activates plasma membrane calcium channels. This, in turn, allows an influx of calcium into the cytosol and NFAT activation. To identify the NFAT controlled apoptosis genes in LPS activated DCs we have performed a kinetic microarray analysis (0, 48 and 60 h) in conditions allowing or inhibiting NFAT activation. Four genes have been selected: Nur77, Gadd45g, Ddit3/Gadd153/Chop-10 and Tia1.
Publication Title
CD14 regulates the dendritic cell life cycle after LPS exposure through NFAT activation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Macrophages and dendritic cells (DCs) differently contribute to the generation of coordinated immune system responses against infectious agents. They interact with microbes through germline-encoded pattern-recognition receptors (PRRs), which recognize molecular patterns expressed by various microorganisms. Upon antigen binding, PRRs instruct DCs for the appropriate priming of natural killer cells, followed by specific T-cell responses. Once completed the effector phase, DCs reach the terminal differentiation stage and eventually die by apoptosis. By contrast, following antigen recognition, macrophages initiate first the inflammatory process and then switch to an anti-inflammatory phenotype for the restoration of tissue homeostasis. Following lipopolysaccharide (LPS)-stimulation the initiation of the apoptotic pathway in DCs is due the activation of NFAT proteins. DC stimulation with lipopolysaccharide (LPS) induces Src-family kinase and phospholipase C (PLC)2 activation, influx of extracellular Ca2+ and calcineurin-dependent nuclear NFAT translocation. The initiation of this pathway is independent of TLR4 engagement, and dependent exclusively on CD14. We asked whether macrophage survival after LPS encounter was due to their inability to activate the Ca2+ pathway.
Publication Title
CD14 regulates the dendritic cell life cycle after LPS exposure through NFAT activation.
Sample Metadata Fields
Specimen part
View Samples