ArticleAlcoholism, clinical and experimental research2015
Chronic Ethanol-Induced Impairment of Wnt/β-Catenin Signaling is Attenuated by PPAR-δ Agonist.
Article in Alcoholism, clinical and experimental research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Alcohol-Associated Hepatocarcinogenesis: Wnt/β-Catenin in Action.The American journal of pathology · 2026Pooled it
- Nuclear hormone receptors control fundamental processes of human fetal neurodevelopment: Basis for endocrine disruption assessment.Environment international · 2025Article
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Differential Early Mechanistic Frontal Lobe Responses to Choline Chloride and Soy Isoflavones in an Experimental Model of Fetal Alcohol Spectrum Disorder.International journal of molecular sciences · 2023Article
- Fatty acid-binding protein 5 aggravates pulmonary artery fibrosis in pulmonary hypertension secondary to left heart disease via activating wnt/β-catenin pathway.Journal of advanced research · 2022Article
- Article
- Acute Intoxication With Alcohol Reduces Trauma-Induced Proinflammatory Response and Barrier Breakdown in the LungFrontiers in immunology · 2022Article
- Binge-Like Ethanol Drinking IncreasesNeuroscience insights · 2021Article
- Alcohol-induced Wnt signaling inhibition during bone fracture healing is normalized by intermittent parathyroid hormone treatment.Animal models and experimental medicine · 2020Article
- Wnt/β-Catenin Signaling in Liver Cancers.Cancers · 2019Review
- Hepatic IRS1 and ß-catenin expression is associated with histological progression and overt diabetes emergence in NAFLD patients.Journal of gastroenterology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe Wnt/β-catenin pathway regulates liver growth, repair, and regeneration. Chronic ethanol (EtOH) exposure blunts normal liver regenerative responses, in part by inhibiting insulin/IGF signaling, and correspondingly, previous studies showed that EtOH-impaired liver regeneration could be restored by insulin sensitizer (proliferator-activated receptor [PPAR]-δ agonist) treatment. As Wnt/β-catenin functions overlap and cross talk with insulin/IGF pathways, we investigated the effects of EtOH exposure and PPAR-δ agonist treatment on Wnt pathway gene expression in relation to liver regeneration.
methodsAdult male Long Evans rats were fed with isocaloric liquid diets containing 0 or 37% EtOH for 8 weeks and also treated with vehicle or a PPAR-δ agonist during the last 3 weeks of the feeding regimen. The rats were then subjected to 70% partial hepatectomy (PH) and livers harvested at various post-PH time points were used to quantitate expression of 19 Wnt pathway genes using Quantigene 2.0 Multiplex Assay.
resultsEtOH broadly inhibited expression of Wnt/β-catenin signaling-related genes, including down-regulation of Wnt1, Fzd3, Lef1, and Bcl9 throughout the post-PH time course (0 to 72 hours), and suppression of Wnt7a, Ccnd1, Fgf4, Wif1, Sfrp2, and Sfrp5 at 18- and 24-hour post-PH time points. PPAR-δ agonist treatments rescued the EtOH-induced suppression of Wnt1, Wnt7a, Fzd3, Lef1, Bcl9, Ccnd1, and Sfrp2 gene expression in liver, corresponding with the improvements in DNA synthesis and restoration of hepatic architecture.
conclusionsChronic high-dose EtOH exposures inhibit Wnt signaling, which likely contributes to the impairments in liver regeneration. Therapeutic effects of PPAR-δ agonists extend beyond restoration of insulin/IGF signaling mechanisms and are mediated in part by enhancement of Wnt pathway signaling. Future studies will determine the degree to which targeted restoration of Wnt signaling is sufficient to improve liver regeneration and remodeling in the context of chronic EtOH exposure.
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