ArticleToxicological sciences : an official journal of the Society of Toxicology2016
Ah Receptor Activation by Dioxin Disrupts Activin, BMP, and WNT Signals During the Early Differentiation of Mouse Embryonic Stem Cells and Inhibits Cardiomyocyte Functions.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Regulation of differentiation and generation of osteoclasts in rheumatoid arthritis.Frontiers in immunology · 2022Pooled it
- Aryl hydrocarbon receptor is involved in DNA damage repair after liver injury with diethylnitrosamine in mice.Molecular biomedicine · 2026Article
- Fine particulate matter‑induced cardiac developmental toxicity (Review).Experimental and therapeutic medicine · 2025Review
- Kynurenic Acid/AhR Signaling at the Junction of Inflammation and Cardiovascular Diseases.International journal of molecular sciences · 2024Review
- The Role of Aryl Hydrocarbon Receptor in Bone Biology.International journal of tryptophan research : IJTR · 2024Review
- AhR and Wnt/β-Catenin Signaling Pathways and Their Interplay.Current issues in molecular biology · 2023Review
- TCDD alters essential transcriptional regulators of osteogenic differentiation in multipotent mesenchymal stem cells.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Activation of the aryl hydrocarbon receptor inhibits neuropilin-1 upregulation on IL-2-responding CD4Frontiers in immunology · 2023Article
- The combined effects of Map3k1 mutation and dioxin on differentiation of keratinocytes derived from mouse embryonic stem cells.Scientific reports · 2022Article
- Review
- Aryl Hydrocarbon Receptor: From Homeostasis to Tumor Progression.Frontiers in cell and developmental biology · 2022Review
- Pathomechanisms of bone loss in rheumatoid arthritis.Frontiers in medicine · 2022Review
- Nuclear Receptors in Myocardial and Cerebral Ischemia-Mechanisms of Action and Therapeutic Strategies.International journal of molecular sciences · 2021Review
- The aryl hydrocarbon receptor promotes differentiation during mouse preimplantational embryo development.Stem cell reports · 2021Article
- Aryl hydrocarbon receptor: Its roles in physiology.Biochemical pharmacology · 2021Review
- AMPKβ1 and AMPKβ2 define an isoform-specific gene signature in human pluripotent stem cells, differentially mediating cardiac lineage specification.The Journal of biological chemistry · 2020Article
- Dioxin Disrupts Dynamic DNA Methylation Patterns in Genes That Govern Cardiomyocyte Maturation.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Impact of AHR Ligand TCDD on Human Embryonic Stem Cells and Early Differentiation.International journal of molecular sciences · 2020Article
- Review
- Human embryonic stem cells as anWorld journal of stem cells · 2020Review
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Authors and funding
9 authors.
Funding
Abstract
The AHR is a ligand-activated transcription factor that mediates gene-environment interactions. Genome-wide expression profiling during differentiation of mouse ES cells into cardiomyocytes showed that AHR activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin; Dioxin (TCDD), its prototypical ligand, disrupted the expression of multiple homeobox transcription factors and inhibited cardiomyocyte contractility. Here we treated ES cells with TCDD at daily differentiation intervals to investigate whether TCDD-induced loss of contractility had a developmental window of sensitivity. Surprisingly, contractility was an AHR-dependent TCDD target solely between differentiation days 0 and 3 during the period of panmesoderm development, when TCDD also disrupted expression of genes in the TGFβ/BMP2/4 and wingless-type MMTV integration site (WNT)signaling pathways, suppressed the secretion of bone morphogenetic protein (BMP4), WNT3a, and WNT5a and elevated the secretion of Activin A, as determined by ELISA of the secreted proteins in the culture medium. Supplementing the culture medium with BMP4, WNT3a, or WNT5a during the first 3 days of differentiation successfully countered TCDD-induced impairment of contractility, while anti-WNT3a, or anti-WNT5a antibodies or continuous Noggin (a BMP4 antagonist) or Activin A treatment inhibited the contractile phenotype. In Ahr(+/+), but not in Ahr(-) (/) (-) ES cells, TCDD treatment significantly increased mitochondrial copy number, suggestive of mitochondrial stress and remodeling. Sustained AHR activation during ES cell differentiation appears to disrupt the expression of signals critical to the ontogeny of cardiac mesoderm and cause the loss of contractility in the resulting cardiomyocyte lineage.
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