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Renal Cyclosporin-A (CsA) toxicity

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE111516 | GEO | 2021/02/22

REPOSITORIES: GEO

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Renal Cyclosporin-A (CsA) toxicity

Project description:Renal Cyclosporin-A (CsA) toxicity

| PRJNA437288 | ENA

Comparative Transcriptional and Phenotypic Peripheral Blood Analysis of Kidney Recipients under Cyclosporin A or Sirolimus Monotherapy

Project description:Due to its low level of nephrotoxicity and capacity to harness tolerogenic pathways, sirolimus (SRL) has been proposed as an alternative to calcineurin inhibitors in transplantation. The exact mechanisms underlying its unique immunosuppressive profile in humans, however, are still not well understood. In the current study we aimed to depict the in vivo effects of SRL in comparison with cyclosporin A (CSA) by employing gene expression profiling and multiparameter flow cytometry on blood cells collected from stable kidney recipients under immunosuppressant monotherapy. SRL recipients displayed an increased frequency of CD4+CD25highFoxp3+ T cells. However, this was accompanied by an increased number of effector memory T cells and by enrichment in NFkB-related pro-inflammatory expression pathways and monocyte and NK cell lineage-specific transcripts. Furthermore, measurement of a transcriptional signature characteristic of operationally tolerant kidney recipients failed to detect differences between SRL and CSA treated recipients. In conclusion, we show here that the blood transcriptional profile induced by SRL monotherapy in vivo does not resemble that of operationally tolerant recipients and is dominated by innate immune cells and NFkB-related pro-inflammatory events. These data provide novel insights on the complex effects of SLR on the immune system in clinical transplantation. The complete database comprised the expression measurements of 54 675 genes for kidney trasplant recipient PBMC treated with SRL (n=23) and CSA (n=14) monotherapy. 9 healthy controls were also included.

2010-10-01 | E-GEOD-22224 | biostudies-arrayexpress

Comparative Transcriptional and Phenotypic Peripheral Blood Analysis of Kidney Recipients under Cyclosporin A or Sirolimus Monotherapy

2010-10-01 | GSE22224 | GEO

Murine Back Skin: Control vs. Cyclosporin A-treated

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

Calcineurin signaling regulates neural induction through antagonizing the BMP pathway

2014-04-01 | GSE54217 | GEO

Cyclosporin A inhibits prostate cancer growth through suppression of E2F8

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

Calcineurin signaling regulates neural induction through antagonizing the BMP pathway

Project description:Calcineurin activity is required for neural differentiation of embryonic stem cells (ESC). We assessed gene expression changes at several time points of in vitro ESC to neural differentiation when calcineurin activity is inhibitied by its antagonist FK506 and Cyclosporin(CsA). d4, d6, d8, and d12 EBs of FK506/CsA treatment group (d3-8) and its non-treated control group were harvested from three independent experiments of in vitro differentiation of 46C mouse ESCs. Total RNA of each sample was extracted, reverse transcribed, labeled and hybridized to Affymetric Mouse Gene ST 1.0 Arrays.

2014-04-01 | E-GEOD-54217 | biostudies-arrayexpress

RNAseq of Calu-3 epithelial cells treated with Cyclosporin A

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

Cyclosporin ameliorates right ventricular remodeling of postnatal mice with volume overload.

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

Differential effects of voclosporin and tacrolimus on insulin secretion from human islets

Project description:The incidence of new onset diabetes after transplant (NODAT) has increased over the past decade, likely due to calcineurin inhibitor-based immunosuppressants, including tacrolimus (TAC) and cyclosporin (CsA). Voclosporin (VCS), a next generation calcineurin inhibitor is reported to cause fewer incidences of NODAT but the reason is unclear. Whilst calcineurin signaling plays important roles in pancreatic beta-cell survival, proliferation, and function, its effects on human beta-cells remain understudied. In particular, we do not understand why some calcineurin inhibitors have more profound effects on the incidence of NODAT. Here, we compared the the effects of TAC and VCS on the transcriptomic profile of human islets.

2020-08-27 | GSE156903 | GEO

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