Microarray expression data from human renal mesangial cells (HMC) treated with a Cyclosporine A (CsA) time course.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE30952 | GEO | 2012/04/04
SECONDARY ACCESSION(S): PRJNA146239
REPOSITORIES: GEO
Similar Datasets
Project description:HMCs were treated with CsA (4.2 M-BM-5M) for 0 12 and 48 hours. To exmaine global gene changes in the renal mesangium following CsA treatment in order to identify novel contributors to CsA-induced renal dysfunction Microarray analysis was used to identify novel mechanisms of CsA nephrotoxicity in the golmerulus Glomerulosceroisis is a key component of overall CsA neophrotxocity. The mesangial cells of the glomerulus are an important cell type with the renal glomerulus. In order to delineate this complex process and identify novel mechanism of the disease and identify possible future therapeutic targets HMCs were treated with CsA for 0 (control) 12 or 48 hours. HMCs were treated with 4.2 M-BM-5M CsA and RNA extracted and hybridised on Affymetrix (HG-U133A) microarrays
2012-04-03 | E-GEOD-30952 | biostudies-arrayexpress
Project description:The calcineurin inhibitor immunosuppressant cyclosporin A (CsA) soon gained clinical application, and became a standard of care in organ transplantation, as well as an important treatment option in a variety of autoimmune diseases. The immunosuppressive effect of CsA is mainly attributed to inhibiting calcineurin phosphatase activity, consequently favouring the inactive phosphorylated form of nuclear factor of activated T cells (NFAT). Renal toxicity is a serious adverse effect of CsA, but the underlying mechanisms are insufficiently understood. CsA has also been shown to induce episodic hypoxia (Fähling et al, 2017; doi: 10.1111/apha.12811). Here, we sought to identify molecular mechanisms of CsA nephrotoxicity.
2021-02-22 | GSE111516 | GEO
Project description:Renal Cyclosporin-A (CsA) toxicity
| PRJNA437288 | ENA
Project description:Effect of 4.2 micromolar Cyclosporine A on human renal proximal tubular cell line HK-2 over 48 hours Keywords: time-course
2004-12-20 | GSE1403 | GEO
Project description:This study represents the first time human kidney endothelial cells were exposed to cyclosporine A (CsA), a calcineurin inhibitor known to contribute to nephrotoxicity with symptoms including microvascular injury. This toxicity has been found to be unique to human trials and human kidneys are particularly susceptible to injury. We found that human kidney peritubular microvascular endothelilal cells (HKMECs) that were exposed to CsA exhibited transcriptomic changes around genes important to VEGF signaling and endothelial inflammation.
2018-12-31 | GSE108919 | GEO
Project description:Chronic calcineurin inhibitor (CNI) nephrotoxicity is a major drawback in current immunosuppressive regimens. Pathology includes vascular and tubulointerstitial alterations. Although still commonly in use, cyclosporine A (CsA) is increasingly exchanged for tacrolimus (Tac) for a more favorable clinical outcome. Data on their differential pathogenetic effects in the kidney are, however, still scarce. We asked how CsA and Tac may affect adverse renal responses differentially. Methods- Wistar rats were divided into groups receiving cyclosporineÊ AÊ (n=4, target trough plasma level 3 mg/ml) and the respective vehicle (n=4, saline), or tacrolimus (Tac, FK506, n= 6, target trough plasma level 3.5 ng/ml) and the respective vehicle (n=6, DMSO/PEG500), via subcutaneously implanted osmotic minipumps for 28 days. Clinical parameters from plasma and urine samples were controlled. Animals were prepared for high-end morphological analysis, elective immunostaining, and high-throughput technology. Large scale electron microscopy (EM), confocal, stimulated emission-depletion (STED) and 3D-structured illumination (SIM) microscopy were used for pathology. Protein biochemistry, transcriptome, proteome, and phosphoproteome technologies were used to identify gene expressional differences. Results - In rats, CsA and Tac produced common as well as distinct alterations in glomeruli and tubulointerstitium. Both drugs caused cortical fibrotic foci with sclerotic glomeruli and damaged tubules. With CsA, glomerular damage was milder than with Tac. Proximal tubules showed widespread dysmorphic lysosomes with peripheral LAMP1 signal as well as autophagic and mitophagic vacuoles along with high apoptosis rate and diminished albumin uptake; megalin-dependent endocytosis was causally involved in the changes, and lysosomal exocytosis was sharply stimulated at the luminal cell pole. KIM1 signal was moderate. With Tac, these changes were far less pronounced, but the incidence of focal tubular necrosis along with intense KIM-1 signal was high. High throughput analysis showed differential changes between CsA and Tac with almost no overlap between the respective spectra. CsA caused upregulation of components of the unfolded protein response and apoptosis, whereas Tac resulted in RAS-associated stimulation and vascular deterioration. Conclusions- CNI nephrotoxicity presented with widely differing pathogenetic characteristics upon chronical CsA vs. Tac treatments. Beyond its known vascular effects, CsA markedly affected proximal tubular integrity, whereas Tac was primarily affecting vascular/glomerular components. Both medications produced comparable degrees of nephron loss and fibrosis. Results may serve to better adjust immunosuppressive treatment combinations in transplant patients.
2024-07-25 | PXD038546 | Pride
Project description:Effect of 4.2 micromolar Cyclosporine A on human renal proximal tubular cell line HK-2 over 48 hours
2008-06-11 | E-GEOD-1403 | biostudies-arrayexpress
Project description:Background- CINAC-patients can be identified by the recently discovered renal proximal tubular cell lysosomal lesions which are also observed in patients experiencing calcineurin inhibitor (CNI) nephrotoxicity, suggesting that CINAC is a toxin-induced nephropathy. An alternative hypothesis advocates chronic heat stress/dehydration as the major etiological factor for CINAC. Here, we evaluated in rats to what extent heat stress/dehydration reflects the renal CINAC histopathology in humans. Methods- Wistar rats were divided in 3 groups. Group 1(n=6) had free access to drinking water (control group). Group 2(n=8) was water deprived for 10 hours per 24hr, 5 days/week and placed in an incubator (37°C) for 30 min/hr during water deprivation. Group 3(n=8) underwent daily oral gavage with cyclosporine (40mg/kg body weight). After 28 days kidneys were collected for light- and electron microscopic histopathology and proteomic analysis. Results- Cyclosporine rats developed renal cortical lesions mimicking those of CINAC patients i.e. atrophic proximal tubules with associated tubulo-interstitial fibrosis. PASM staining demonstrated enlarged argyrophilic granules in the affected proximal tubules, identified as lysosomes by LAMP1 immunofluorescent staining. Electron microscopy confirmed the presence of enlarged dysmorphic lysosomes, closely mimicking the dysmorphic lysosomes seen in CINAC-patients. Dehydration was demonstrated by urinary osmolality and fluctuating body weight but showed none of the histological features of CINAC patients. Proteomic analysis confirmed cellular toxicity of cyclosporine, whereas the dehydration group lacked any of these toxicity markers. Conclusion- Dehydration/heat stress alone does not lead to the renal proximal tubular and interstitial lesions as observed in CINAC-patients. The histopathological analogy between CINAC and CNI nephrotoxicity in rats and humans and CINAC supports the toxicological etiology.
2022-11-14 | PXD038062 | Pride
Project description:IgA nephropathy (IgAN) is the most common glomerulonephritis in the world. The disease is characterized by galactose deficient IgA (gd-IgA) in the circulation forming immune complexes. The complexes are deposited in the glomerular mesangium leading to inflammation and loss of renal function, but the pathophysiology of the disease is still not fully understood. Using an integrated global transcriptomic and proteomic profiling approach we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsies from patients with IgAN. The influence of galactose deficient IgA (gd-IgA) on mesangial cells was investigated by proteomic profiling. By utilizing the previous published literature curated glomerular cell type-specific genes, we found that mesangial cells and their positive standard genes play a more dominant role in IgAN comparing to the podocyte standard genes. Additionally, the patient clinical parameters (serum creatinine values and estimated glomerular filtration rate - eGFR) significantly correlate with z-scores derived from expression profile of mesangial cell positive standard genes. 22 common pathways were identified both from in vivo microarray data and in vitro mesangial cell mass spectrometry data and the main part was inflammatory pathways. The correlation between clinical data and mesangial standard genes allows for a better understanding of the onset of IgAN. The genes, proteins and their corresponding pathways identified in this paper give us novel insights into the pathophysiological mechanisms leading to progression of IgAN. RNA from glomerular compartment was extracted and processed for hybridization on Affymetrix microarrays. This dataset is part of the TransQST collection.
2017-07-03 | E-GEOD-93798 | biostudies-arrayexpress
Project description:IgA nephropathy (IgAN) is the most common glomerulonephritis in the world. The disease is characterized by galactose deficient IgA (gd-IgA) in the circulation forming immune complexes. The complexes are deposited in the glomerular mesangium leading to inflammation and loss of renal function, but the pathophysiology of the disease is still not fully understood. Using an integrated global transcriptomic and proteomic profiling approach we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsies from patients with IgAN. The influence of galactose deficient IgA (gd-IgA) on mesangial cells was investigated by proteomic profiling. By utilizing the previous published literature curated glomerular cell type-specific genes, we found that mesangial cells and their positive standard genes play a more dominant role in IgAN comparing to the podocyte standard genes. Additionally, the patient clinical parameters (serum creatinine values and estimated glomerular filtration rate - eGFR) significantly correlate with z-scores derived from expression profile of mesangial cell positive standard genes. 22 common pathways were identified both from in vivo microarray data and in vitro mesangial cell mass spectrometry data and the main part was inflammatory pathways. The correlation between clinical data and mesangial standard genes allows for a better understanding of the onset of IgAN. The genes, proteins and their corresponding pathways identified in this paper give us novel insights into the pathophysiological mechanisms leading to progression of IgAN.
2017-07-03 | GSE93798 | GEO