Transcription profiling of mouse kidney treated with with vancomycin to assess nephrotoxicity
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Hanna Ng
PROVIDER: E-GEOD-7793 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The glycopeptide antibiotic vancomycin (VCM) represents one of the last lines of defense against methicillin-resistant Staphylococcus aureus infections. However, vancomycin is nephrotoxic, but the mechanism of toxicity is still unclear. The goal of this study was twofold: (1) gain insights into the molecular mechanisms of vancomycin nephrotoxicity at the genomic level and (2) evaluate potential biomarkers (gene expression profiles) of vancomycin-induced kidney injury Keywords: Dose response
2008-10-23 | GSE7793 | GEO
Project description:The objective of this study is to analyze miRNA profiling in the kidneys of rats gavaged with OTA. To profile miRNAs in the kidneys of rats with OTA nephrotoxicity, high-throughput sequencing and bioinformatics approaches were applied to analyze the miRNAs in the kidney of rats following OTA treatment
2014-06-01 | E-MTAB-2475 | biostudies-arrayexpress
Project description:Cephaloridine (CER) is a classical beta-lactam antibiotic that has long served as a model drug for the study of cephalosporin antibiotic-induced acute tubular necrosis. In the present study, we analyzed gene expression profiles in the kidney of rats given subtoxic and toxic doses of CER in order to identify gene expression alterations closely associated with CER-induced nephrotoxicity. Male Fisher 344 rats were intravenously injected with three different doses (150, 300, and 600 mg/kg) of CER, and sacrificed after 24 h. Only the high dose (600 mg/kg) caused mild proximal tubular necrosis and a slight renal dysfunction. Microarray analysis identified hundreds of genes differentially expressed in the renal cortex following the exposure to CER, which could be classified into two main groups that were deregulated in dose-dependent and high dose-specific manners. The genes upregulated dose-dependently mainly included those involved in detoxification and antioxidant defense, which was considered to be associated with CER-induced oxidative stress. In contrast, the genes showing high dose-specific (lesion-specific) induction included a number of genes related to cell proliferation, which appeared to reflect a compensatory response to CER injury. We also found a subset of G2/M phase genes that exhibited hormesis-like (U-Shape) biphasic dose response; namely, downregulation only at the low and/or middle (subtoxic) doses. Furthermore, we could predict potential transcription regulators responsible for the observed gene expression alterations, such as Nrf2 and E2F family. Among the candidate gene biomarkers, kidney injury molecule 1 was markedly upregulated at the mildly toxic dose, suggesting that this gene can be used as an early and sensitive indicator for cephalosporin nephrotoxicity. In conclusion, our transcriptomic data revealed several characteristic expression patterns of genes associated with specific cellular processes, including oxidative stress response and proliferative response, upon exposure to CER, which may enhance our understandings of molecular mechanisms behind cephalosporin antibiotic-induced nephrotoxicity. Keywords: compound treatment, dose response In the present study, we acquired gene expression profiles in the kidney of rats given subtoxic and toxic doses of cephaloridine (CER) using whole-genome oligonucleotide microarrays. Male rats were injected with vehicle alone and three different doses (150, 300, and 600 mg/kg) of CER, and sacrificed after 24 h. Each dose group contained 3 animals.
2010-05-26 | E-GEOD-10034 | biostudies-arrayexpress
Project description:Cisplatin induces both acute and chronic nephrotoxicity during chemotherapy in cancer patients. Here, we report the study of single-nucleus sequencing (snRNA-seq) of cisplatin-induced nephrotoxicity.
2023-08-05 | GSE239749 | GEO
Project description:Biomarkers for aristolochic acid nephrotoxicity
| PRJNA680917 | ENA
Project description:Polymyxin nephrotoxicity in kidney chip
| PRJNA508797 | ENA
Project description:Ochratoxin A (OTA) is one of the most abundant mycotoxin contaminants in food stuffs and possesses carcinogenic, nephrotoxic, teratogenic and immunotoxic properties. Especially, severe nephrotoxicity is of great concern, as characterized by degeneration of epithelial cells of the proximal tubules and interstitial fibrosis. However, its mechanism of toxicity, hazard identification as well as genetic risk factors contributing to OTA toxicity in humans has been elusive due to the lack of adequate models that fully recapitulate kidney function in vitro. The present study attempts to evaluate dose-response relationships, identify the contribution of active transport proteins that govern renal disposition of OTA, and determine the role of metabolism in bioactivation and detoxification of OTA using a 3D human kidney proximal tubule microphysiological system (kidney MPS). We demonstrated that IC50 values of OTA in kidney MPS culture (0.375 – 1.21 µM) were in good agreement with clinical toxic concentrations of OTA in urine. Surprisingly, no enhancement of kidney injury biomarkers was evident in the effluents of kidney MPS after OTA exposure despite significant toxicity observed by LIVE/DEAD staining, rather these biomarkers were decreased in OTA concentration-dependent manner. Furthermore, the effect of 1-aminobenzotriazole (ABT) and 6-(NBD-4-ylthio-) hexanol (NBDHEX), pan-inhibitor of P450 and GST enzymes, respectively, on the OTA-induced toxicity in kidney MPS was examined, which resulted in significant enhancement of OTA-induced toxicity by NBDHEX (3 µM) treatment whereas ABT (1 mM) treatment decreased OTA-induced toxicity, suggesting the roles of GSTs and P450 enzymes in the detoxification and bioactivation of OTA, respectively. Additionally, OTA transport studies using kidney MPS in the presence and absence of inhibitor of organic anion transporter(s), probenecid (1 mM), revealed the role of organic anionic membrane transporter(s) in the kidney specific disposition of OTA. Our findings provide a better understanding of the mechanism of OTA-induced kidney injury which may support changes in risk assessment, regulatory agency policies on allowable exposure levels and determination of genetic factors in high-risk populations against OTA nephrotoxicity.
2020-10-22 | GSE151776 | GEO
Project description:Far infrared radiation (FIR), a subdivision of the electromagnetic spectrum, has been proved to be beneficial for long-term effects of tissue healing, anti-inflammation, promoting growth, modulating sleep, acceleration of microcirculation, and pain relief. We attempt to study whether FIR would be beneficial for renal proximal tubule cell (RPTC) cultivation and renal tissue engineering. We observed the FIR effects on RPTCs, including cell viability, functional characteristics, immunofluorescence presentations, and subcellular findings. And the FIR protective effects would be further examined with HK-2 cell (Human proximal tubule cell line) against cisplatin, a nephrotoxic agent. Our study showed that daily exposure to FIR for 30 minutes could significantly increase rabbit RPTC viability in vitro assessed by MTT assay. FIR is not only beneficial in RPTC cell viability. RPTCs with FIR exposure presented higher expression of Na-K ATPase and GLUT1 (Glucose Transporter 1). The finding was documented with western blot analysis with statistical significance. With Q-PCR, CDK5R1, GNAS, NPPB, and TEK expressions were significantly enhanced. With HK-2 cell, the proximal tubule cell line, FIR had protective effects against cisplatin nephrotoxicity through reducing apoptosis. FIR is a potential photomodulation therapy to facilitate RPTC cultivation with higher cell viability and better functional chanacteristics and would possibly be applied in further nephrotoxicity protection and other cisplatin-sensitive cell protection.
2017-09-05 | GSE98096 | GEO
Project description:Although Tacrolimus is an immunosuppressive drug widely used in renal transplantation, its chronic use paradoxically induces nephrotoxic effects, in particular renal fibrosis, which is responsible for chronic allograft dysfunction and represents a major prognostic factor of allograft survival. As molecular pathways and mechanisms involved in Tacrolimus-induced fibrogenic response are poorly elucidated, we assessed whether miRNAs are involved in the nephrotoxic effects mediated by Tacrolimus. Treatment of CD-1 mice with Tacrolimus (1mg/kg/d for 28 days) resulted in kidney injury and was associated with alteration of a gene expression signature associated with cellular stress, fibrosis and inflammation. Tacrolimus also affected renal miRNA expression, including miRNAs previously involved in fibrotic and inflammatory processes including “fibromirs” such as miR-21-5p. Specifically, Renal Proximal Tubular Epithelial cells exposed to tacrolimus showed up-regulation of miR-21-5p and the concomitant induction of epithelial phenotypic changes, inflammation and oxidative stress. In conclusion, this study suggests for the first time that miRNAs, especially fibromiRs, mediate Tacrolimus-induced nephrotoxic effects. This SuperSeries is composed of the SubSeries listed below.
2018-02-06 | GSE102515 | GEO
Project description:Although Tacrolimus is an immunosuppressive drug widely used in renal transplantation, its chronic use paradoxically induces nephrotoxic effects, in particular renal fibrosis, which is responsible for chronic allograft dysfunction and represents a major prognostic factor of allograft survival. As molecular pathways and mechanisms involved in Tacrolimus-induced fibrogenic response are poorly elucidated, we assessed whether miRNAs are involved in the nephrotoxic effects mediated by Tacrolimus. Treatment of CD-1 mice with Tacrolimus (1mg/kg/d for 28 days) resulted in kidney injury and was associated with alteration of a gene expression signature associated with cellular stress, fibrosis and inflammation. Tacrolimus also affected renal miRNA expression, including miRNAs previously involved in fibrotic and inflammatory processes including “fibromirs” such as miR-21-5p. Specifically, Renal Proximal Tubular Epithelial cells exposed to tacrolimus showed up-regulation of miR-21-5p and the concomitant induction of epithelial phenotypic changes, inflammation and oxidative stress. In conclusion, this study suggests for the first time that miRNAs, especially fibromiRs, mediate Tacrolimus-induced nephrotoxic effects.
2018-02-06 | GSE102514 | GEO