Comparison of gene expression in AhR WT (+/+) and AhR KO (-/-) primary mouse keratinocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE62490 | GEO | 2015/07/01
SECONDARY ACCESSION(S): PRJNA264282
REPOSITORIES: GEO
Similar Datasets
Project description:The AhR is a ligand activated transcription factor that may be important in normal skin physiology. We compared gene expression profiles between AhR Wt and AhR KO primary mouse keratinocyte cultures. We identified 391 genes that were differentially expressed with a 1.5 fold cutoff and p<.05, and identified the AhR as an important regulator of genes involved in normal epidermal differentiation. AhR Wt primary keratinocyte cultures (n=4) were compared with AhR KO primary keratinocyte cultures (n=3)
2015-07-01 | E-GEOD-62490 | biostudies-arrayexpress
Project description:Atopic dermatitis is increasing worldwide, correlating with air pollutions. Various organic components of pollutants activate transcription factor AhR (aryl-hydrocarbon receptor). We have established AhR-CA mice, whose keratinocytes express constitutive-active AhR, and these mice developed atopic dermatitis-like frequent scratching and allergic inflammation. In this study we performed ChIP-seq analyses and identified keratinocyte-specific AhR target genes, including inflammatory cytokines Tslp and IL33, and neurotrophic factor Artemin. While AhR-CA mice exhibited epidermal hyperinnervation and alloknesis leading to hypersensitivity to pruritus, blockade of Artemin alleviated these phenotypes. AhR-CA mice showed scratching-induced barrier insufficiency and enhanced sensitization to epicutaneously-applied antigens, recapitulating human atopic dermatitis. Consistently, AhR activation and Artemin expression was detected in the epidermis of atopic dermatitis patients and keratinocytes exposed to air pollutants. Thus, AhR in keratinocytes senses the environmental stimuli and responds to them through moderating inflammation. We propose a mechanism in which air pollution induces atopic dermatitis through AhR activation.
2016-11-13 | GSE72455 | GEO
Project description:Occupational and environmental exposure to polycyclic aromatic hydrocarbons (PAHs) has been suggested to provoke inflammatory and/or allergic disorders including asthma, rhinitis and dermatitis. The molecular mechanisms of this PAH-mediated inflammation remain to be clarified. Previous studies implied the involvement of PAHs as irritants and allergens, with the reactive oxygen species generated from the oxygenated PAHs believed to be an exacerbating factor. As well, the possibility exists that PAHs contribute to the pathogenesis through activation of aryl-hydrocarbon receptor (AhR)-mediated transcription, since PAHs are potent inducers of the AhR. To address this point, we generated transgenic mouse lines expressing the constitutive active form of the AhR in keratinocytes. In these lines of mice, the AhR activity was constitutively enhanced in the absence of ligands, so that any other direct effects of PAHs and their metabolites could be ignored. At birth, these transgenic mice were normal, but severe skin lesions with itching developed postnatally. The skin lesions were accompanied by inflammation and immunological imbalance and resembled typical atopic dermatitis. Our present study demonstrates that constitutive activation of the AhR pathway causes inflammatory skin lesions and suggests a new mechanism for the exacerbation of inflammatory diseases following exposure to occupational and environmental xenobiotics. Keywords: transcriptional activation
2005-10-01 | GSE2955 | GEO
Project description:Occupational and environmental exposure to polycyclic aromatic hydrocarbons (PAHs) has been suggested to provoke inflammatory and/or allergic disorders including asthma, rhinitis and dermatitis. The molecular mechanisms of this PAH-mediated inflammation remain to be clarified. Previous studies implied the involvement of PAHs as irritants and allergens, with the reactive oxygen species generated from the oxygenated PAHs believed to be an exacerbating factor. As well, the possibility exists that PAHs contribute to the pathogenesis through activation of aryl-hydrocarbon receptor (AhR)-mediated transcription, since PAHs are potent inducers of the AhR. To address this point, we generated transgenic mouse lines expressing the constitutive active form of the AhR in keratinocytes. In these lines of mice, the AhR activity was constitutively enhanced in the absence of ligands, so that any other direct effects of PAHs and their metabolites could be ignored. At birth, these transgenic mice were normal, but severe skin lesions with itching developed postnatally. The skin lesions were accompanied by inflammation and immunological imbalance and resembled typical atopic dermatitis. Our present study demonstrates that constitutive activation of the AhR pathway causes inflammatory skin lesions and suggests a new mechanism for the exacerbation of inflammatory diseases following exposure to occupational and environmental xenobiotics. Experiment Overall Design: transgenic mice expressing constitutive active form of AhR in keratinocytes vs. non-transgenic mice (wild type littermates)
2008-06-12 | E-GEOD-2955 | biostudies-arrayexpress
Project description:Atopic dermatitis is increasing worldwide, correlating with air pollutions. Various organic components of pollutants activate transcription factor AhR (aryl-hydrocarbon receptor). We have established AhR-CA mice, whose keratinocytes express constitutive-active AhR, and these mice developed atopic dermatitis-like frequent scratching and allergic inflammation. In this study we performed ChIP-seq analyses and identified keratinocyte-specific AhR target genes, including inflammatory cytokines Tslp and IL33, and neurotrophic factor Artemin. While AhR-CA mice exhibited epidermal hyperinnervation and alloknesis leading to hypersensitivity to pruritus, blockade of Artemin alleviated these phenotypes. AhR-CA mice showed scratching-induced barrier insufficiency and enhanced sensitization to epicutaneously-applied antigens, recapitulating human atopic dermatitis. Consistently, AhR activation and Artemin expression was detected in the epidermis of atopic dermatitis patients and keratinocytes exposed to air pollutants. Thus, AhR in keratinocytes senses the environmental stimuli and responds to them through moderating inflammation. We propose a mechanism in which air pollution induces atopic dermatitis through AhR activation.
2016-11-13 | GSE72449 | GEO
Project description:The Aryl Hydrocarbon Receptor (AHR) is an environmental sensor and an indispensable regulator of epithelial homeostasis. To investigate AHR-mediated gene regulation, we performed a comprehensive transcriptomic and epigenomic analysis using human primary epidermal keratinocytes. Our results showed that AHR activation led to the induction of canonical transcription factors involved in epidermal differentiation as an early response, i.e. Transcription Factor AP-2α (TFAP2A), while epidermal differentiation-related genes, such as filaggrin and keratins, were activated as late responsive genes. The identified AHR-TFAP2A axis and its role in keratinocyte terminal differentiation was confirmed through AHR and TFAP2A knockout using CRISPR/Cas9. Our findings demonstrate that AHR regulates epidermal differentiation through the transient activation of specific transcription factors, such as TFAP2A, in response to environmental cues. The herein identified AHR-TFAP2A axis provides a promising target for the treatment of diseases related to skin barrier dysfunction.
2023-09-08 | GSE226046 | GEO
Project description:The Aryl Hydrocarbon Receptor (AHR) is an environmental sensor and an indispensable regulator of epithelial homeostasis. To investigate AHR-mediated gene regulation, we performed a comprehensive transcriptomic and epigenomic analysis using human primary epidermal keratinocytes. Our results showed that AHR activation led to the induction of canonical transcription factors involved in epidermal differentiation as an early response, i.e. Transcription Factor AP-2α (TFAP2A), while epidermal differentiation-related genes, such as filaggrin and keratins, were activated as late responsive genes. The identified AHR-TFAP2A axis and its role in keratinocyte terminal differentiation was confirmed through AHR and TFAP2A knockout using CRISPR/Cas9. Our findings demonstrate that AHR regulates epidermal differentiation through the transient activation of specific transcription factors, such as TFAP2A, in response to environmental cues. The herein identified AHR-TFAP2A axis provides a promising target for the treatment of diseases related to skin barrier dysfunction.
2023-09-08 | GSE226045 | GEO
Project description:Sometimes biological research is an act of faith, a belief that untangling complex biologic interactions on a very basic level in-and-of itself eventually leads to larger and broader implications for human health. Indeed, sometimes focusing on the trees leads to a better view of the forest. This has been the case for the aryl hydrocarbon receptor (AHR). For decades, the AHR was studied for its role in environmental chemical toxicity i.e., as a quirk of nature and a mediator of unintended consequences of human pollution. During that period, it was not certain that the AHR had a “normal” physiological function. However, the ongoing accumulation of data from an ever-expanding variety of studies on cancer, cancer immunity, autoimmunity, organ development, and other areas bears witness to a staggering array of AHR-controlled normal and pathological activities. The objective of this review is to discuss how the AHR has gone from a likely contributor to genotoxic environmental carcinogen-induced cancer to a master regulator of malignant cell progression and cancer aggression. Particular focus was placed on the association between AHR activity and poor outcomes, feedback loops that control chronic AHR activity in cancer, and the role of chronically active AHR in driving cancer cell invasion, migration, cancer stem cell characteristics, and survival.
2023-12-11 | GSE163859 | GEO
Project description:The transcriptional program of early embryonic development is tightly regulated by a set of well-defined transcription factors that suppress premature expression of differentiation genes and sustain the pluripotent identity. It is generally accepted that this program can be perturbed by environmental factors such as chemical pollutants, however the precise molecular mechanisms remain unknown. The Aryl Hydrocarbon Receptor (AHR) is a widely expressed nuclear receptor that senses environmental stimuli and modulates target gene expression. Here, we show that ectopic activation of AHR during early differentiation disrupts the differentiation program via the chromatin remodeling complex NuRD. The activated AHR/NuRD complex altered the expression of differentiation-specific genes that control the first two developmental decisions without affecting the pluripotency program. These findings identify a novel mechanism that allows environmental stimuli to disrupt embryonic development through AHR signaling.
2018-02-26 | PXD006089 | Pride