Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-39812
PROVIDER: PRJNA171764 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Tryptamine Serves As a Proligand of the AhR Transcriptional Pathway, and the Activation Is Dependent of Monoamine Oxidases
2019-05-14 | E-GEOD-39812 | ExpressionAtlas
Project description:Transcriptional activation of AhR pathway in keratinocytes
| PRJNA92433 | ENA
Project description:The Aryl Hydrocarbon Receptor (AHR) regulates the expression of numerous genes in response to activation by agonists including xenobiotics. Although it is well appreciated that environmental signals and cell intrinsic features may modulate this transcriptional response, how it is mechanistically achieved remains poorly understood. We show that Hexokinase 2 (HK2) a metabolic enzyme fuelling cancer cell growth, is a transcriptional target of AHR as well as a modulator of its activity. Expression of HK2 is positively regulated by AHR upon exposure to agonists both in human cells and in mice lung tissues. Conversely, over-expression of HK2 regulates the abundance of many proteins involved in the regulation of AHR signalling and these changes are linked with altered AHR expression levels and transcriptional activity. HK2 expression also shows a negative correlation with AHR promoter methylation in tumours, and these tumours with high HK2 expression and low AHR methylation are associated with a worse overall survival in patients. In sum, our study provides novel insights into how AHR signalling is regulated which may help our understanding of the context-specific effects of this pathway and may have implications in cancer.
2022-05-31 | PXD028992 | Pride
Project description:Wild-type and AHR-KO rats harboring a 29-bp deletion mutation in exon 2 of the AHR gene were used in this study. Wild-type and AHR-KO rats were generated from heterozygous breeding stocks generated on a Sprague-Dawley outbred background and maintained at the Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina Persistent activation of the aryl hydrocarbon receptor (AHR) is believed to play a key role in the mode-of-action for TCDD induced rat liver tumorigenesis. It has been hypothesized that the cellular responses of hepatocytes to AHR activation may differ across regions of the liver lobule and that zone-specific effects of AHR agonists may play a role in the pathogenesis of rat liver tumorigenesis. Dose-dependent changes in gene expression were observed in both populations of hepatocytes collected from WT rats which were consistent with activation of AHR signaling. No significant or dose-dependent changes in gene expression were observed in samples from AHR-KO rats. In addition, evidence of inflammatory signaling pathway activation was observed only in centrilobular hepatocytes. Evidence of cell adhesion pathway enrichment was observed only in periportial hepatocytes. Benchmark dose analysis demonstrated that dose-dependent changes in gene expression occurred at lower doses in centrilobular as compared to periportal hepatocytes. These results indicate zone-specific differences in the sensitivity and response of hepatocytes to persistent AHR activation. AHR-KO and WT rats (n = 10 rats/dose/genotype) were dosed by oral gavage (4-5 doses / week, 19 total doses) with varying concentrations of TCDD in corn oil (0, 3, 22, 100, 300, 1000 ng/kg/day). Cryopreserved liver slices collected at necropsy were thawed, cryosectioned (12 µm thickness), fixed with ethanol and âquick-stainedâ with hematoxylin. Centrilobular and periportal hepatocytes were collected using laser capture microdissection. Total RNA was extracted, amplified and labeled using low-yield techniques and global transcriptomic profiles were obtained using Affymetrix Gene-Titan peg arrays.
2016-09-01 | E-GEOD-72506 | biostudies-arrayexpress
Project description:Wild-type and AHR-KO rats harboring a 29-bp deletion mutation in exon 2 of the AHR gene were used in this study. Wild-type and AHR-KO rats were generated from heterozygous breeding stocks generated on a Sprague-Dawley outbred background and maintained at the Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina Persistent activation of the aryl hydrocarbon receptor (AHR) is believed to play a key role in the mode-of-action for TCDD induced rat liver tumorigenesis. It has been hypothesized that the cellular responses of hepatocytes to AHR activation may differ across regions of the liver lobule and that zone-specific effects of AHR agonists may play a role in the pathogenesis of rat liver tumorigenesis. Dose-dependent changes in gene expression were observed in both populations of hepatocytes collected from WT rats which were consistent with activation of AHR signaling. No significant or dose-dependent changes in gene expression were observed in samples from AHR-KO rats. In addition, evidence of inflammatory signaling pathway activation was observed only in centrilobular hepatocytes. Evidence of cell adhesion pathway enrichment was observed only in periportial hepatocytes. Benchmark dose analysis demonstrated that dose-dependent changes in gene expression occurred at lower doses in centrilobular as compared to periportal hepatocytes. These results indicate zone-specific differences in the sensitivity and response of hepatocytes to persistent AHR activation.
2016-09-01 | GSE72506 | GEO
Project description:Exposures to dioxin, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cause a wide array of toxicities in vertebrates and is mostly considered to be mediated through the inappropriate activation of the aryl hydrocarbon receptor (Ahr) signaling pathway. Although transcriptional regulation by Ahr is widely studied, the molecular mechanisms responsible for the adverse outcomes after Ahr activation are largely unknown. To identify the important events downstream of AHR activation that play an actual role in the toxic responses, we employed the zebrafish caudal fin regeneration models since Ahr activation blocks the regenerative process. Zebrafish regenerate their caudal fins by an orchestrated progression of cell migration, differentiation and proliferation controlled by a multitude of signaling pathways. This complex process was exploited as an in vivo platform to identify cross talk between Ahr and other signaling pathways. Global genomic analysis was performed in the larval regenerating fin tissue after exposure to TCDD in order to identify genes differentially regulated after Ahr activation. Comparative toxicogenomic analysis revealed that both adult and larval fins respond to TCDD during regeneration with mis-expression of Wnt signaling pathway members and Wnt target genes. Experiment Overall Design: The caudal fin of zebrafish larvae at 2days post fertilization were amputated and exposed to vehicle control alone or TCDD. Regenerating fins were isolated at 2and 3 days post amputation. Three replicates were collected at each time point. 150 fins were pooled to comprise one replicate.
2008-04-07 | E-GEOD-10184 | biostudies-arrayexpress
Project description:Exposures to dioxin, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cause a wide array of toxicities in vertebrates and is mostly considered to be mediated through the inappropriate activation of the aryl hydrocarbon receptor (Ahr) signaling pathway. Although transcriptional regulation by Ahr is widely studied, the molecular mechanisms responsible for the adverse outcomes after Ahr activation are largely unknown. To identify the important events downstream of AHR activation that play an actual role in the toxic responses, we employed the zebrafish caudal fin regeneration models since Ahr activation blocks the regenerative process. Zebrafish regenerate their caudal fins by an orchestrated progression of cell migration, differentiation and proliferation controlled by a multitude of signaling pathways. This complex process was exploited as an in vivo platform to identify cross talk between Ahr and other signaling pathways. Global genomic analysis was performed in the larval regenerating fin tissue after exposure to TCDD in order to identify genes differentially regulated after Ahr activation. Comparative toxicogenomic analysis revealed that both adult and larval fins respond to TCDD during regeneration with mis-expression of Wnt signaling pathway members and Wnt target genes. Keywords: comparative toxico-genomics
2008-02-29 | GSE10184 | GEO
Project description:Although the tumor promoting effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), coplanar polychlorinated biphenyls (PCBs) and related compounds in liver tissue are primarily attributed to activation of the aryl hydrocarbon receptor (AhR), the underlying molecular mechanisms are still unclear. Liver progenitor (oval) cells have been suggested to constitute a potential target for hepatocarcinogenic chemicals. To better understand AhR-driven pathways we analyzed the transcriptional program in response to coplanar PCB 126 in rat liver progenitor WB-F344 cells using high density microarrays. After 6h treatment, we identified 145 significantly deregulated genes considered to be direct AhR-dependent target genes. The number of differentially regulated genes increased to 658 and 968 genes after 24h and 72h, respectively. Gene ontology analysis revealed that these genes were primarily involved in drug and lipid metabolism, cell cycle and growth control, cancer developmental processes, cell-cell communication and adhesion. Interestingly, the Wnt and TGF-beta signaling pathways, both being involved in developmental and tumorigenic processes, belonged to the most affected pathways. AhR and ARNT-dependent regulation of selected target genes of interest was then confirmed using TCDD as a model AhR agonist, together with pharmacological inhibition of the AhR and by RNA-interference techniques. We demonstrated AhR-dependent regulation of emerging and novel AhR target genes, such as Fst, Areg, Hbegf, Ctgf, Btg2, and Foxq1. Among them, the transcription factor Foxq1, recently suggested to contribute to tumor promotion and/or progression, was found to be regulated at both mRNA and protein levels by AhR/ARNT activation. 18 Total samples were analyzed (3 independent repeats for each treatment and time point). We generated the following pairwise comparisons: Control vs. PCB 126 at 6 h; Control vs. PCB 126 at 24 h; Control vs. PCB 126 at 72 h;
2013-05-01 | E-GEOD-41902 | biostudies-arrayexpress
Project description:AhR activation by TCDD in the ET, cortical epithelial cell line
| PRJNA108369 | ENA
Project description:In this study we show that physiological concentrations of tryptamine (TA) lead to induction of cytochrome P4501A1 transcription through an AhR-dependent mechanism. In addition, we show that activation of the AhR by TA requires a functional monoamino oxidase system, suggesting that TA acts as an AhR proligand possibly by converting to a high-affinity AhR ligand. RNA seq was performed from Hepa cells treated with FICZ or TA by SciLifelabs.
2012-08-02 | E-GEOD-39812 | biostudies-arrayexpress