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Endogenous aryl hydrocarbon receptor ligands-dysregulated transcriptomic profiles and endothelial function in human fetal endothelial cells

ABSTRACT: Endogenous aryl hydrocarbon receptor ligands-dysregulated transcriptomic profiles and endothelial function in human fetal endothelial cells

PROVIDER: PRJNA1052652 | ENA |

REPOSITORIES: ENA

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Endogenous aryl hydrocarbon receptor ligands-dysregulated transcriptomic profiles and endothelial function in human fetal endothelial cells

Project description:Preeclampsia (PE) is a hypertensive disorder and a leading cause of maternal and fetal mortality and morbidity during human pregnancy. Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, regulates vascular development and function during pregnancy. Here, we report the important role of endogenous AhR ligands in endothelial growth and function during pregnancy using human umbilical vein endothelial cells (HUVECs) as a model. We found that ITE, ([2-(1’H-indole-3’-carbonyl)-thiazole-4-carboxylic acid methyl ester], an endogenous AhR ligand) decreased cell proliferation and monolayer integrity in HUVECs in vitro. ITE also dysregulated transcriptomic profiles of HUVECs in a fetal sex-specific manner. The ITE-dysregulated genes were enriched in biological function and pathways highly relevant to cardiovascular diseases, vascular function, and inflammation responses. We conclude that dysregulation of endogenous AhR ligands may contribute to the PE-impaired endothelial function through fetal sex-specific regulation of endothelial transcriptomes. These AhR ligand-activated genes and pathways might represent promising therapeutic and sex-specific targets for PE-impaired endothelial function.

2025-02-10 | GSE250196 | GEO

Endogenous aryl hydrocarbon receptor ligands-dysregulated transcriptomic profiles and vascular function in rat placentas

Project description:Preeclampsia (PE) is a hypertensive disorder and a leading cause of maternal and fetal mortality and morbidity during human pregnancy. Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, regulates vascular development and function during pregnancy. Here, we report the important role of endogenous AhR ligands in vascular growth and function during pregnancy using a rat model. We found that exposure of pregnant rats to an endogenous AhR ligand (ITE, [2-(1’H-indole-3’-carbonyl)-thiazole-4-carboxylic acid methyl ester]) elevated maternal blood pressure and induced proteinuria, while decreased uteroplacental blood flow and fetal/ placental growth, all of which are hallmarks of PE. ITE also dysregulated transcriptomic profiles of rat placentas in a fetal sex-specific manner. The ITE-dysregulated genes were enriched in biological function and pathways highly relevant to diseases of heart, liver, and kidney, vascular function, and inflammation responses. Collectively, we conclude that dysregulation of endogenous AhR ligands may contribute to the PE-impaired vascular function through fetal sex-specific regulation of immune cell infiltration and transcriptomes. These AhR ligand-activated genes and pathways might represent promising therapeutic and sex-specific targets for PE-impaired vascular function.

2025-02-10 | GSE250269 | GEO

Endogenous aryl hydrocarbon receptor ligands-dysregulated transcriptomic profiles and vascular function in rat placentas

Project description:Endogenous aryl hydrocarbon receptor ligands-dysregulated transcriptomic profiles and vascular function in rat placentas

| PRJNA1053275 | ENA

Zebrafish larvae aryl hydrocarbon receptor ligands and inhibitor

Project description:Zebrafish larvae aryl hydrocarbon receptor ligands and inhibitor

| PRJNA495640 | ENA

Effect of canonical aryl hydrocarbon receptor pathway inhibitor on human umbilical vein endothelial cells

Project description:To study the effect of blockade of canonical aryl hydrocarbon receptor (AHR) pathway in human endothelial cells, we treated human umbilical vein endothelial cells (HUVECs) with a canonical AHR inhibitor, Stemreginin 1 (SR1) and performed bulk RNAseq analysis.

2024-07-01 | GSE251861 | GEO

Zebrafish larvae aryl hydrocarbon receptor ligands and inhibitor

Project description:Wild type zebrafish (AB strain, https://zfin.org/action/genotype/view/ZDB-GENO-960809-7) were set up for mating overnight, in 3:2 ratios, females and males, respectively. Fertilized embryos from wildtype zebrafish AB strain were used for all experiments and kept in Embryo medium (E3, 5 mM NaCl, 0.17 mM KCl, 0.33 mM CaCl2, 0.33 mM MgSO4) in an incubator at 28ºC. At 1dpf, larvae were manually dechorionated under a stereomicroscope. At 2dpf, zebrafish larvae were divided randomly into the different experimental groups, at a density of 12 larvae per well of a 12 well plate (Corning) in 1.5mL of E3. Three biological replicates of 12 larvae per condition were exposed to different conditions for 4 hours at 28 ºC: DMSO; DMSO + CH223191 (5mM); 3-o-C12-L-HSL (50mM); 3-o-C12-L-HSL (50mM) + CH223191 (5 mM ); 1-hydroxyphenazine (1-HP, 5mM); 1-HP (5mM) + CH223191(5mM) and 1-HP (5mM) + 3-o-C12-L-HSL (50mM).To mention, in experiments using the Aryl hydrocarbon Receptor inhibitor CH223191, larvae were pre-exposed to 5uM of the inhibitor for 2h prior to the start of the experiment and the inhibitor was kept during the experiment. After the desired exposure to diverse ligands, larvae were euthanized with Tricaine (MS-222, 300 µg/mL) and placed in Trizol for RNA isolation. The same experimental layout was performed 5 times, and samples were subjected to microarray hybridization and analysis.

2019-10-01 | GSE121101 | GEO

Aryl Hydrocarbon Receptor Ligands Present In The Environment Impact Human Trophoblast Cell Development

Project description:Aryl Hydrocarbon Receptor Ligands Present In The Environment Impact Human Trophoblast Cell Development

| PRJNA1033546 | ENA

Lead optimization of aryl hydrocarbon receptor ligands for treatment of inflammatory skin disorders

Project description:Lead optimization of aryl hydrocarbon receptor ligands for treatment of inflammatory skin disorders

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Ancestralization of the modern human aryl hydrocarbon receptor by genome editing

Project description:The aryl hydrocarbon receptor (AHR) is a transcription factor that upon binding ligands induces the expression of cytochrome P450 genes, which encode enzymes that metabolize aromatic hydrocarbons. The AHR carries an amino acid substitution at position 381 in all present-day humans that occurred after the divergence of modern humans from Neandertals and Denisovans. Here, we use genome editing to revert position 381 back to the ancestral state in human cells. Cells were treated with ligands for 4 h followed by RNA extraction and RNA-Seq.

2024-06-26 | GSE210514 | GEO

Aryl Hydrocarbon Receptor Ligands Present In The Environment Impact Human Trophoblast Cell Development [EVT]

Project description:Aryl Hydrocarbon Receptor Ligands Present In The Environment Impact Human Trophoblast Cell Development [EVT]

| PRJNA1033543 | ENA