Renal Cyclosporin-A (CsA) toxicity
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ABSTRACT:
PROVIDER: PRJNA437288 | ENA |
REPOSITORIES: ENA
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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:HMCs were treated with CsA (4.2 µM) 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
2012-04-04 | GSE30952 | GEO
Project description:We analyzed the gene expression at the onset of hair growth induced by cyclosporin A (CsA), a well-known hair growth inducer, with DNA microarray, and unveiled the step-by-step progression of hair growth. KEYWORDS: Cyclosporin A, Cyclosporine A, Ciclosporin A
2009-12-24 | GSE16739 | GEO
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:Cyclosporin A (CsA) is a potent immunosuppressive agent used clinically in organ transplantation. In this study, we examined that CsA exerts anti-tumor activity against prostate cancer. We performed microarray experiments to investigate the effect of CsA on the transcriptome of prostate cancer cells. CsA potently induced transcriptome change and primarily affected cell cycle-related gene signatures. These results suggest that CsA can be used as a potential therapeutic agent or an intriguing tool for exploring prostate cancer biology and identifying novel therapeutic targets.
2023-10-04 | GSE109505 | GEO
Project description:Calu-3 cells are human lung cancer cells that serve as a model of respiratory epithelial cell model. Here, Calu-3 cells are used as a cell system for Middle East respiratory syndrome coronavirus and treated with Cyclosporin A To assess the effect of Cyclosporin A on the host cells, uninfected cells were treated with CsA or DMSO, RNA was extracted and compared against the DMSO treated control cells.
2020-08-01 | E-MTAB-8222 | biostudies-arrayexpress
Project description:The transcription factor farnesoid X receptor (FXR) governs bile acid and energy homeostasis, is involved in inflammation, and has protective functions in the liver. In the present study we investigated the effect of Fxr deficiency in mouse precision cut liver slices (PCLS) exposed to a model hepatotoxicant cyclosporin A (CsA). It was anticipated that Fxr deficiency could aggravate toxicity of CsA in PCLS and pinpoint to novel genes/processes regulated by FXR. To test this hypothesis, PCLS obtained from livers of wild type mice (WT-PCLS) and Fxr-knockout mice (FXRKO-PCLS) were treated with 40µM CsA for 24h and 48h. ATP and histological assays were applied to assess the viability of PCLS. DNA microarrays combined with bioinformatics analysis were used to identify genes and processes that were affected by CsA in WT-PCLS and/or FXRKO-PCLS. In addition, WT-PCLS and FXRKO-PCLS were exposed to the endogenous FXR ligand chenodeoxycholic acid (CDCA) and subjected to q-PCR to determine whether subsets of known FXR-targets and the identified genes were regulated upon FXR activation in an FXR-dependent manner. No difference in viability was observed between WT-PCLS and FXRKO-PCLS upon CsA treatment. Transcriptomics data analysis revealed that CsA significantly upregulated stress-response and inflammation and significantly downregulated processes involved in lipid and glucose metabolism in both WT-PCLS and FXRKO-PCLS. However, only in FXRKO-PCLS, CsA upregulated additional pro-inflammatory genes and downregulated genes related to mitochondrial functions. Furthermore, only in WT-PCLS, CDCA upregulated a subset of known FXR-target genes as well as the regulator of inflammation and mitochondrial functions peroxisome proliferator- activated receptor delta (Ppar delta). Although FXR governs energy metabolism, no major differences in response to CsA could be observed between WT-PCLS and FXRKO-PCLS in regulation of processes involved in lipid and glucose metabolism. This finding indicates that CsA does not directly affect FXR functions in relation to the above mentioned processes. However, the more pronounced induction of pro-inflammatory genes and the downregulation of genes involved in mitochondrial functions only in FXRKO-PCLS suggest that FXR deficiency aggravates CsA-induced inflammation and impairs mitochondrial functions. Therefore, FXR can exert its hepatoprotective functions by controlling inflammation and mitochondrial functions, possibly involving an FXR-PPAR delta cross-talk. Precision cut liver slices (PCLS) obtained from livers of wild type (WT) and farnesoid X receptor knockout (FXRKO) mice were exposed for 24 hours to 40uM of CyclosporinA (CsA).
2015-10-22 | GSE63457 | GEO
Project description:We reported the RNAseq analyses of right ventricular free wall of myocardium in three groups of mice（3 in each group）at postnatal day 14 (P14). The mice in volume overload (VO) group underwent an abdominal surgery by puncture from aorta to inferior vena cava at P7, mice in Sham group underwent the same surgery except for the puncture. The mice in CsA group were VO mice who were also injected with cyclosporin A(CsA) for seven days. The results revealed that there were differentially expressed genes between VO and sham group at P14, Inhibiting the immune response with CsA caused the gene expression profile of VO mice to shift towards that of sham mice.
2024-02-01 | GSE254207 | GEO
Project description:Mechanism-based toxicogenomics (tgx) is used as a tool to identify markers reflective of the onset and progression of cholestasis in C57BL/6 mice using Cyclosporin A (CsA) as a model compound. Critical doses for tgx analysis were derived from a dose range finding study in which increase of serum cholesterol, total bile acids, and total bilirubin as well as induction of hepatocyte vacuolization 25 days upon repeated CsA administration through oral gavage were considered as critical effects. For tgx analysis to find early markers, livers of mice repeatedly treated with 3 mg/kg BW, 8.9 mg/kg BW, and 26.7 mg/kg BW for one, four, and eleven days were collected.
2013-07-11 | GSE31540 | GEO
Project description:Cyclophilin binding drugs, NIM811 and cyclosporin A (CsA), inhibit the replication of HCV replicon. We investigated the mode of action of these drugs and identified host factors essential for HCV replication in a subgenomic replicon model. Experiment Overall Design: Cultured Huh7 cell were treated with CsA or NIM811 at different concentrations. Cells were harvested after 12, 24 or 48 hours. The extracted mRNA were hybridized on Affymetrix U133 Plus 2 microarrays.
2009-05-11 | E-GEOD-15935 | biostudies-arrayexpress