Identification of genes showing altered DNA methylation and gene expression in the renal proximal tubular cells of rats treated with ochratoxin A for 13 weeks
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE231379 | GEO | 2024/09/30
REPOSITORIES: GEO
Similar Datasets
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:Microarrays were used to analyse gene expression underlying early tumourigenesis in Eker rats. Distinct classes of up- and downregulated genes were identified in different preneoplasic lesion vs. microdissected normal (healthy) renal tubules. Laser capture microdissected renal basophilic atypical tubule (bAT) and basophilic atypical hyperplasia (bAH) and healthy tissue (HT) of 6-months aristolochic acid (AA)- and ochratoxin A (OTA)-treated and control (C) male Eker rats were isolated for RNA extraction and microarray analysis in order to investigate gene expression profiles induced by AA and OTA as well as to differentiate pathways specific for the bAT to bAH progression. Keywords: gene expression study, preneoplasic lesion vs. microdissected normal renal tubules
2010-02-20 | GSE10608 | GEO
Project description:Microarrays were used to analyse gene expression underlying early tumourigenesis in Eker rats. Distinct classes of up- and downregulated genes were identified in different preneoplasic lesion vs. microdissected normal (healthy) renal tubules. Laser capture microdissected renal basophilic atypical tubule (bAT) and basophilic atypical hyperplasia (bAH) and healthy tissue (HT) of 6-months aristolochic acid (AA)- and ochratoxin A (OTA)-treated and control (C) male Eker rats were isolated for RNA extraction and microarray analysis in order to investigate gene expression profiles induced by AA and OTA as well as to differentiate pathways specific for the bAT to bAH progression. Keywords: gene expression study, preneoplasic lesion vs. microdissected normal renal tubules For microdissection of preneoplastic lesions from H&E stained renal cryosections, a PALM laser microdissection and pressure catapulting (LMPC) system (PALM Microlaser GmbH) was used. Atypical tubule (bAT), basophilic atypical hyperplasia (bAH) or healthy tissue (HT) were micodissected separately from each of three replicatemale Eker rats per dose group. Lesions of each type or HT from each individual animal were pooled. RNA isolation from pooled samples and subsequent Affymetrix Rat Genome RAE_230A_2.0 chip hybridization was carried out as previously described (Stemmer et al., Toxicology and Applied Pharmacology(2006) Nov 15;217(1):134-42). Time matched controls for microarrays from lesions of OTA and AA treated rats are specified as C(AA) and C(OTA).
2010-02-28 | E-GEOD-10608 | biostudies-arrayexpress
Project description:Ochratoxin A (OTA) is a fungal secondary metabolite widely found in cereal and a wide variety of foods; it also exhibits carcinogenic effects, nephrotoxicity, and teratogenicity. In this study, the zebrafish was applied to investigate the effects of ochratoxin A on gene expressions in zebrafish embryos.
2018-07-16 | GSE71345 | GEO
Project description:Changes in renal gene expression were assessed in p53WT(+/+) mice and their heterozygous p53TG(+/-) counterparts exposed to the nephrotoxic and tumourigenic fungal toxin Ochratoxin A (OTA) in their diet for 26 weeks. The p53TG mouse model has been used in screening for potential carcinogens as it displays increased sensitivity to genotoxic carcinogens. Comparison between the effects of OTA in diet on male mice of these two strains was assessed at 0, 0.05, 2.0, 10.0 mg OTA/kg diet. Changes in global gene expression were compared using Agilent Mouse oligonucleotide microarray analysis of kidneys from control (0 mg OTA/kg diet) and treated (2 mg OTA/kg diet) mice. Significant changes in gene expression associated with cell cycle regulation, DNA damage repair, tumour suppression and apoptosis were consistent with nephrotoxicity due to OTA exposure in both mouse strains. Changes in genes related to oxidative stress and free radical scavenging may contribute to the down-regulation by OTA of genes associated with metabolism. Gene expression changes were consistent with phenotype and provided insight on the cellular responses to chronic OTA exposure.
2016-10-28 | GSE89256 | GEO
Project description:Renal gene expression profiles of Eker and wild type rats, gavaged with AA or OTA, respectively for 1, 3, 7 or 14 days We used Affymetrix RAE230A microarrays for the analysis of early gene expression changes in the renal cortex_ outer medulla of carcinogen treated Eker and corresponding wild type rats Keywords: time course
2007-08-23 | GSE5923 | GEO
Project description:Renal gene expression profiles of Eker and wild type rats, gavaged with AA or OTA, respectively for 1, 3, 7 or 14 days; We used Affymetrix RAE230A microarrays for the analysis of early gene expression changes in the renal cortex_ outer medulla of carcinogen treated Eker and corresponding wild type rats Experiment Overall Design: Eker and wild type rats were gavaged daily with OTA (210µg_ kg BW) or AA (10mg_ kg BW), dissolved in 0,1M sodium bicarbonate. Time-matched vehicle controls were gavaged with 0,1M sodium bicarbonate. Following 1, 3, 7, and 14 days of treatment, Narcoren (pentobarbital) anesthetized rats were sacrificed by exsanguination subsequent to retrograde perfusion with PBS. Left kidneys were collected, cross-sectioned into 5mm slices and stored in RNAlater for subsequent RNA isolantion and chip hybridisation
2008-06-14 | E-GEOD-5923 | biostudies-arrayexpress
Project description:The aim of this study was to reveal the genomic response of yeast cells to the related mycotoxins citrinin (CIT) and ochratoxin A (OTA). Both mycotoxins can be produced by the same filamentous fungi and co-contaminate the same foodstuff. However, it is not known whether CIT and OTA share the same toxicity mechanisms or not. We performed transcriptomic profiling experiments using microarray hybridization of a pdr5 mutant strain exposed separately to CIT or OTA and exposed to a combination of both toxins. A yeast pdr5 mutant was used, because it is significantly sensitized to both toxins. We find that CIT and OTA cause the rapid activation of largely non-overlapping gene sets. The most prominent functional group of CIT-activated genes corresponds to the cellular response to oxidative stress, while OTA-activated genes belong predominantly to single organism developmental processes and meiosis/sporulation. The combined exposure of CIT and OTA revealed a mixed response of functional gene groups. Our results demonstrate that CIT and OTA have distinguishable and independent biological effects with oxidative stress being a hallmark for CIT toxicity and the deregulation of developmental genes being the principal feature for OTA toxicity.
2016-10-01 | GSE84187 | GEO
Project description:Ochratoxin A (OTA) is a nephrotoxin that has been associated with kidney damages. The goal of this project was to identified which impact had nanomolar concentrations of this toxin on cells derived from human kidney in order to identify putative key regulators and underlying mechanisms of the already described phenotypes (e.g. increased apoptosis, dysregulated cell cycle)
2020-01-15 | GSE133831 | GEO
Project description:We report the transcriptome and miRNAome of human embryonic kidney 293 cells upon the administration of ochratoxin A (OTA) and citrinin (CTN), to compare the individual and combined toxicity of these two mycotoxins. We identified largely differentially expressed miRNAs and corresponding genes, and the correlations between miRNAs and their target genes associated with apoptotic signaling were furthermore analyzed by pmi-RB-REPORT luciferase assay system. We concluded that hsa-miR-1-3p plays an essential role in promoting OTA and CTN-induced renal cytotoxicity.
2017-12-31 | GSE93148 | GEO