ArticleiScience2018
Aryl Hydrocarbon Receptor Promotes Liver Polyploidization and Inhibits PI3K, ERK, and Wnt/β-Catenin Signaling.
Article in iScience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 34 citations in OpenAlex.
- Aryl hydrocarbon receptor is involved in DNA damage repair after liver injury with diethylnitrosamine in mice.Molecular biomedicine · 2026Article
- Six-compound cocktail for maturation of human pluripotent stem cell-derived liver spheroids for toxicity prediction.Nature communications · 2026Article
- FOXM1 inhibition primes terminal differentiation of human iPSC-derived hepatocytes.Cell death discovery · 2026Article
- Aryl hydrocarbon receptor: a multifaceted environmental sensor in liver homeostasis and disease.Frontiers in medicine · 2026Review
- AHR Deficiency Exacerbates Hepatic Cholesterol Accumulation via Inhibiting Bile Acid Synthesis in MAFLD Rats.International journal of molecular sciences · 2025Article
- Application of a metabolic network-based graph neural network for the identification of toxicant-induced perturbations.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- The aryl hydrocarbon receptor in liver injury: a double-edged sword in roles, mechanisms, and future perspectives.Frontiers in pharmacology · 2025Review
- Activation of AHR by ITE improves cardiac remodelling and function in rats after myocardial infarction.ESC heart failure · 2023Article
- Induction of Aryl Hydrocarbon Receptor-Mediated Cancer Cell-Selective Apoptosis in Triple-Negative Breast Cancer Cells by a High-Affinity Benzimidazoisoquinoline.ACS pharmacology & translational science · 2023Article
- Molecular networking identifies an AHR-modulating benzothiazole from white button mushrooms (Journal of functional foods · 2023Article
- AhR and Wnt/β-Catenin Signaling Pathways and Their Interplay.Current issues in molecular biology · 2023Review
- Tumor-Suppressive Functions of the Aryl Hydrocarbon Receptor (AhR) and AhR as a Therapeutic Target in Cancer.Biology · 2023Review
- Single-cell transcriptomics shows dose-dependent disruption of hepatic zonation by TCDD in mice.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- From Nucleus to Organs: Insights of Aryl Hydrocarbon Receptor Molecular Mechanisms.International journal of molecular sciences · 2022Review
- Liver regeneration after partial hepatectomy is improved in the absence of aryl hydrocarbon receptor.Scientific reports · 2022Article
- Article
- Aryl hydrocarbon receptor blocks aging-induced senescence in the liver and fibroblast cells.Aging · 2022Article
- Identification of Modulators of theAntioxidants (Basel, Switzerland) · 2022Article
- The interplay of aryl hydrocarbon receptor/WNT/CTNNB1/Notch signaling pathways regulate amyloid beta precursor mRNA/protein expression and effected the learning and memory of mice.Toxicology research · 2022Article
- Aryl Hydrocarbon Receptor: From Homeostasis to Tumor Progression.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
Aryl hydrocarbon receptor (AhR) deficiency alters tissue homeostasis. However, how AhR regulates organ maturation and differentiation remains mostly unknown. Liver differentiation entails a polyploidization process fundamental for cell growth, metabolism, and stress responses. Here, we report that AhR regulates polyploidization during the preweaning-to-adult mouse liver maturation. Preweaning AhR-null (AhR-/-) livers had smaller hepatocytes, hypercellularity, altered cell cycle regulation, and enhanced proliferation. Those phenotypes persisted in adult AhR-/- mice and correlated with compromised polyploidy, predominance of diploid hepatocytes, and enlarged centrosomes. Phosphatidylinositol-3-phosphate kinase (PI3K), extracellular signal-regulated kinase (ERK), and Wnt/β-catenin signaling remained upregulated from preweaning to adult AhR-null liver, likely increasing mammalian target of rapamycin (mTOR) activation. Metabolomics revealed the deregulation of mitochondrial oxidative phosphorylation intermediates succinate and fumarate in AhR-/- liver. Consistently, PI3K, ERK, and Wnt/β-catenin inhibition partially rescued polyploidy in AhR-/- mice. Thus, AhR may integrate survival, proliferation, and metabolism for liver polyploidization. Since tumor cells tend to be polyploid, AhR modulation could have therapeutic value in the liver.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.