Involvement of aryl hydrocarbon receptor nuclear translocator in EGF-induced c-Jun/Sp1-mediated gene expression

2010 ◽  
Vol 67 (20) ◽  
pp. 3523-3533 ◽  
Author(s):  
Wan-Chen Huang ◽  
Shu-Ting Chen ◽  
Wei-Chiao Chang ◽  
Kwang-Yu Chang ◽  
Wen-Chang Chang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aryl Hydrocarbon Receptor ◽  
Aryl Hydrocarbon

scholarly journals Neuronal activity enhances aryl hydrocarbon receptor-mediated gene expression and dioxin neurotoxicity in cortical neurons

2008 ◽  
Vol 104 (5) ◽  
pp. 1415-1429 ◽  
Author(s):  
Chun-Hua Lin ◽  
Shu-Hui Juan ◽  
Chen Yu Wang ◽  
Yu-Yo Sun ◽  
Chih-Ming Chou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aryl Hydrocarbon Receptor ◽  
Neuronal Activity ◽  
Cortical Neurons ◽  
Aryl Hydrocarbon

scholarly journals Nascent RNA sequencing defines dynamic aryl hydrocarbon receptor signaling responses to wood smoke particles

2021 ◽  
Author(s):  
Arnav Gupta ◽  
Sarah K. Sasse ◽  
Lynn Sanford ◽  
Margaret A. Gruca ◽  
Robin D. Dowell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aryl Hydrocarbon Receptor ◽  
Airway Epithelial Cells ◽  
Wood Smoke ◽  
Primary Role ◽  
Airway Epithelial ◽  
Transcriptional Responses ◽  
Wildfire Smoke ◽  
Smoke Particles ◽  
Aryl Hydrocarbon

AbstractTranscriptional responses to wildfire smoke, an increasingly important cause of human morbidity, are poorly understood. Here, using a combination of precision nuclear run-on sequencing (PRO-seq) and the assay for transposase-accessible chromatin using sequencing (ATAC-seq), we identify rapid and dynamic changes in transcription and chromatin structure in Beas-2B airway epithelial cells after exposure to wood smoke particles (WSP). By comparing 30 and 120 minutes of WSP exposure, we defined three distinct temporal patterns of transcriptional induction and chromatin responses to WSP. Whereas transcription of canonical targets of the aryl hydrocarbon receptor (AHR), such as CYP1A1 and AHRR, was robustly increased after 30 minutes of WSP exposure, transcription of these genes and associated enhancers returned to near baseline at 120 minutes. ChIP-qPCR assays and AHR knockdown confirmed a role for AHR in regulating these transcriptional responses, and we applied bioinformatics approaches to identify novel AHR-regulated pathways and targets including the DNA methyltransferase, DNMT3L, and its interacting factor, SPOCD1. Our analysis also defined a role for NFkB as a primary transcriptional effector of WSP-induced changes in gene expression. The kinetics of AHR- and NFkB-regulated responses to WSP were distinguishable based on the timing of both transcriptional responses and chromatin remodeling, with induction of several cytokines implicated in maintaining the NFkB response. In aggregate, our data establish a direct and primary role for AHR in mediating airway epithelial responses to WSP and identify crosstalk between AHR and NFkB signaling in controlling pro-inflammatory gene expression.

scholarly journals Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes during Experimental Liver Fibrosis

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Cheri L. Lamb ◽  
Giovan N. Cholico ◽  
Daniel E. Perkins ◽  
Michael T. Fewkes ◽  
Julia Thom Oxford ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Liver Injury ◽  
Aryl Hydrocarbon Receptor ◽  
Receptor Activation ◽  
Matrix Remodeling ◽  
Mrna Levels ◽  
Gelatinase Activity ◽  
Ecm Remodeling ◽  
Aryl Hydrocarbon

The aryl hydrocarbon receptor (AhR) is a soluble, ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Increasing evidence implicates the AhR in regulating extracellular matrix (ECM) homeostasis. We recently reported that TCDD increased necroinflammation and myofibroblast activation during liver injury elicited by carbon tetrachloride (CCl4). However, TCDD did not increase collagen deposition or exacerbate fibrosis in CCl4-treated mice, which raises the possibility that TCDD may enhance ECM turnover. The goal of this study was to determine how TCDD impacts ECM remodeling gene expression in the liver. Male C57BL/6 mice were treated for 8 weeks with 0.5 mL/kg CCl4, and TCDD (20 μg/kg) was administered during the last two weeks. Results indicate that TCDD increased mRNA levels of procollagen types I, III, IV, and VI and the collagen processing molecules HSP47 and lysyl oxidase. TCDD also increased gelatinase activity and mRNA levels of matrix metalloproteinase- (MMP-) 3, MMP-8, MMP-9, and MMP-13. Furthermore, TCDD modulated expression of genes in the plasminogen activator/plasmin system, which regulates MMP activation, and it also increased TIMP1 gene expression. These findings support the notion that AhR activation by TCDD dysregulates ECM remodeling gene expression and may facilitate ECM metabolism despite increased liver injury.

scholarly journals Screening a mouse liver gene expression compendium identifies modulators of the aryl hydrocarbon receptor (AhR)

Toxicology ◽  
2015 ◽  
Vol 336 ◽  
pp. 99-112 ◽  
Author(s):  
Keiyu Oshida ◽  
Naresh Vasani ◽  
Russell S. Thomas ◽  
Dawn Applegate ◽  
Frank J. Gonzalez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aryl Hydrocarbon Receptor ◽  
Mouse Liver ◽  
Aryl Hydrocarbon ◽  
Liver Gene

scholarly journals Disruption of endogenous regulator homeostasis underlies the mechanism of rat CYP1A1 mRNA induction by metyrapone

1998 ◽  
Vol 331 (1) ◽  
pp. 273-281 ◽  
Author(s):  
Joanna L. HARVEY ◽  
Alan J. PAINE ◽  
Matthew C. WRIGHT
Keyword(s):  
Gene Expression ◽  
Glucocorticoid Receptor ◽  
Aryl Hydrocarbon Receptor ◽  
Culture Medium ◽  
Male Rats ◽  
Aryl Hydrocarbon ◽  
Mrna Induction ◽  
Cyp1a1 Gene ◽  
Cyp1a1 Mrna

The transcriptional induction of the cytochrome P-450 1A1 (CYP1A1) gene by xenobiotics such as polyaromatic hydrocarbons is dependent on their interaction with the aryl hydrocarbon receptor. Administration of the structurally unrelated compounds metyrapone (a cytochrome P-450 inhibitor) or dexamethasone (a glucocorticoid) to male rats does not induce hepatic CYP1A1 mRNA. However, administration of both metyrapone and dexamethasone to male rats results in the induction of hepatic CYP1A1 mRNA expression. The induction response is mimicked in vitro in cultured rat hepatocytes by the addition of metyrapone and dexamethasone to a serum-free culture medium, suggesting that these compounds act directly on the liver in vivo to effect hepatic CYP1A1 mRNA induction. An examination of the characteristics of CYP1A1 induction by metyrapone and dexamethasone in combination in vitro indicate that at least 6 h of treatment is required for detectable levels of CYP1A1 mRNA to accumulate in hepatocytes. In contrast, β-naphthoflavone, which is known to bind to the aryl hydrocarbon receptor to effect CYP1A1 gene expression, induces detectable levels of CYP1A1 mRNA within 2 h of treatment. CYP1A1 mRNA is also induced when hepatocytes are treated with metyrapone in combination with the protein synthesis inhibitor cycloheximide but not with dexamethasone in combination with cycloheximide, indicating that CYP1A1 mRNA induction is strictly dependent on the presence of metyrapone and suggesting that the metyrapone-associated induction of CYP1A1 mRNA is dependent on a loss of a constitutively expressed protein that functions to suppress CYP1A1 gene expression. The role of dexamethasone in metyrapone-associated induction of CYP1A1 is probably mediated through the glucocorticoid receptor since the glucocorticoid receptor antagonist RU486 reduces the levels of CYP1A1 mRNA induced by metyrapone and dexamethasone in combination. Increasing the levels of the photosensitizer riboflavin present in the culture medium 10-fold and exposure to light increases the levels of CYP1A1 mRNA induced by metyrapone and dexamethasone in combination in vitro, suggesting that photoactivation of inducing medium constituent(s) might be required for induction. Failure to induce CYP1A1 mRNA by co-administration of metyrapone and dexamethasone in hepatocytes cultured in a balanced salt solution with or without photoactivation indicates that induction is dependent on a photoactivated component of the culture medium and not on metyrapone or dexamethasone alone. The addition of tryptophan in the presence of riboflavin to the balanced salt solution restores CYP1A1 mRNA induction by metyrapone alone and induction is increased when medium is exposed to light, indicating that induction is dependent on tryptophan photoactivation in vitro. Metyrapone failed to compete with 2,3,7,8-tetrachlorodibenzo-p-dioxin for specific binding to the aryl hydrocarbon receptor in rat liver cytosolic fractions. These results suggest that CYP1A1 might be induced in rats by metyrapone through an indirect mechanism associated with an elevation in the level of an endogenously generated inducer such as photoactivated product(s) of tryptophan and not because of metyrapone's interacting with the aryl hydrocarbon receptor. The dependence of CYP1A1 induction on dexamethasone or cycloheximide suggests that derepression by a glucocorticoid receptor-modulated negative-acting factor of CYP1A1 gene expression might be critical to induction by metyrapone.

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