ArticleToxicological sciences : an official journal of the Society of Toxicology2016
Dose-Dependent Metabolic Reprogramming and Differential Gene Expression in TCDD-Elicited Hepatic Fibrosis.
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 48 papers.
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Who cites it
48 citing papers in PubMed, 66 citations in OpenAlex.
- Aryl hydrocarbon receptor pharmacology-mechanisms, ligands, and therapeutic potential.Pharmacological reviews · 2026Review
- Cell type- and species-specific regulation of hepatic lncRNAs by TCDD-activated aryl hydrocarbon receptor.Scientific reports · 2025Article
- Hepatic AhR Activation by TCDD Induces Obesity and Steatosis via Hepatic Plasminogen Activator Inhibitor-1 (PAI-1).International journal of molecular sciences · 2025Article
- Shift in the urinary metabolome associated with 2,3,7,8-tetrachlorodibenzo-p-dioxin activation of the hepatic aryl hydrocarbon receptor.Scientific reports · 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
- Analysis of systemic effects of dioxin on human health through template-and-anchor modeling.PLoS computational biology · 2025Article
- Application of Single Cell Methods in Immunometabolism and Immunotoxicology.Current opinion in toxicology · 2024Article
- Cell-specific AHR-driven differential gene expression in the mouse liver cell following acute TCDD exposure.BMC genomics · 2024Article
- Identification of potential biomarkers from amino acid transporter in the activation of hepatic stellate cells via bioinformatics.Frontiers in genetics · 2024Article
- The potential of aryl hydrocarbon receptor as receptors for metabolic changes in tumors.Frontiers in oncology · 2024Review
- Hepatic cholesterol biosynthesis and dioxin-induced dysregulation: A multiscale computational approach.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2023Article
- Aggravated hepatic fibrosis induced by phenylalanine and tyrosine was ameliorated by chitooligosaccharides supplementation.iScience · 2023Article
- Characterizing the impact of simvastatin co-treatment of cell specific TCDD-induced gene expression and systemic toxicity.Scientific reports · 2023Article
- TCDD dysregulation of lncRNA expression, liver zonation and intercellular communication across the liver lobule.Toxicology and applied pharmacology · 2023Article
- Cystine/Glutamate XcChemical research in toxicology · 2023Article
- Consequences of reprogramming acetyl-CoA metabolism by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the mouse liver.Scientific reports · 2023Article
- TCDD dysregulation of lncRNA expression, liver zonation and intercellular communication across the liver lobule.bioRxiv : the preprint server for biology · 2023Article
- Cinnabarinic Acid Provides Hepatoprotection Against Nonalcoholic Fatty Liver Disease.The Journal of pharmacology and experimental therapeutics · 2022Article
- Article
- Hexokinase 2 is a transcriptional target and a positive modulator of AHR signalling.Nucleic acids research · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
We have previously shown that in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-elicited NAFLD progression, central carbon, glutaminolysis, and serine/folate metabolism are reprogrammed to support NADPH production and ROS defenses. To further investigate underlying dose-dependent responses associated with TCDD-induced fibrosis, female C57BL/6 mice were gavaged with TCDD every 4 days (d) for 28 d or 92 d. RNA-Seq, ChIP-Seq (2 h), and 28 d metabolomic (urine, serum, and hepatic extract) analyses were conducted with complementary serum marker assessments at 92 d. Additional vehicle and 30 µg/kg treatment groups were allowed to recover for 36 d following the 92-d treatment regimen to examine recovery from TCDD-elicited fibrosis. Histopathology revealed dose-dependent increases in hepatic fat accumulation, inflammation, and periportal collagen deposition at 92 days, with increased fibrotic severity in the recovery group. Serum proinflammatory and profibrotic interleukins-1β, -2, -4, -6, and -10, as well as TNF-α and IFN-γ, exhibited dose-dependent induction. An increase in glucose tolerance was observed with a concomitant 3.0-fold decrease in hepatic glycogen linked to increased ascorbic acid biosynthesis and proline metabolism, consistent with increased fibrosis. RNA-Seq identified differential expression of numerous matrisome genes including an 8.8-fold increase in Tgfb2 indicating myofibroblast activation. Further analysis suggests reprogramming of glycogen, ascorbic acid, and amino acid metabolism in support of collagen deposition and the use of proline as a substrate for ATP production via the proline cycle. In summary, we demonstrate that glycogen, ascorbic acid, and amino acid metabolism are also reorganized to support remodeling of the extracellular matrix, progressing to hepatic fibrosis in response to chronic injury from TCDD.
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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.