ArticleAntioxidants & redox signaling2015
WNT-3A regulates an Axin1/NRF2 complex that regulates antioxidant metabolism in hepatocytes.
Article in Antioxidants & redox signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 60 citations in OpenAlex.
- The interplay between vitamin D3 and Nrf2 signaling: mechanistic insights and therapeutic potentials.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- L-DOPA enhances iRPE differentiation via Wnt signaling and improves cytotherapy for retinal degradation.Stem cell research & therapy · 2026Article
- Neuroprotection From Intracerebral Hemorrhage Following Pharmacological Inhibition of GSK3β Depends on HFE Gene Status.Journal of neurochemistry · 2026Article
- Integrative analysis of KEAP1/NFE2L2 alterations across 3600+ tumors reveals an NRF2 expression signature as a prognostic biomarker in cancer.NPJ precision oncology · 2025Article
- The Role of the Wnt/β-Catenin Pathway in the Modulation of Doxorubicin-Induced Cytotoxicity in Cardiac H9c2 Cells by Sulforaphane and Quercetin.International journal of molecular sciences · 2025Article
- A novel β-TrCP1/NRF2 interaction inhibitor for effective anti-inflammatory therapy.Journal of biomedical science · 2025Article
- Axin formation inhibitor 1 aggravates hepatic ischemia‒reperfusion injury by promoting the ubiquitination and degradation of PPARβ.Nature communications · 2025Article
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
- Loss of β-catenin reveals a role for glutathione in regulating oxidative stress during cholestatic liver disease.Hepatology communications · 2024Article
- A dual model of normal vs isogenic Nrf2-depleted murine epithelial cells to explore oxidative stress involvement.Scientific reports · 2024Article
- Selenium Deficiency Exacerbates Hyperoxia-Induced Lung Injury in Newborn C3H/HeN Mice.Antioxidants (Basel, Switzerland) · 2024Article
- The scaffold protein AXIN1: gene ontology, signal network, and physiological function.Cell communication and signaling : CCS · 2024Review
- G9a and Sirtuin6 epigenetically modulate host cholesterol accumulation to facilitate mycobacterial survival.PLoS pathogens · 2023Article
- Advances in Understanding the Role of NRF2 in Liver Pathophysiology and Its Relationship with Hepatic-Specific Cyclooxygenase-2 Expression.Antioxidants (Basel, Switzerland) · 2023Review
- TRIB1 regulates liver regeneration by antagonizing the NRF2-mediated antioxidant response.Cell death & disease · 2023Article
- Nrf2 induces malignant transformation of hepatic progenitor cells by inducing β-catenin expression.Redox biology · 2022Article
- Epigallocatechin-3-gallate suppresses hemin-aggravated colon carcinogenesis through Nrf2-inhibited mitochondrial reactive oxygen species accumulation.Journal of veterinary science · 2022Article
- β1,4-Galactosyltransferase V Modulates Breast Cancer Stem Cells through Wnt/β-catenin Signaling Pathway.Cancer research and treatment · 2020Article
- A conditional mouse expressing an activating mutation in NRF2 displays hyperplasia of the upper gastrointestinal tract and decreased white adipose tissue.The Journal of pathology · 2020Article
- Nrf2/Wnt resilience orchestrates rejuvenation of glia-neuron dialogue in Parkinson's disease.Redox biology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
aimsNuclear factor (erythroid-derived 2)-like 2 (NRF2) is a master regulator of oxidant and xenobiotic metabolism, but it is unknown how it is regulated to provide basal expression of this defense system. Here, we studied the putative connection between NRF2 and the canonical WNT pathway, which modulates hepatocyte metabolism.
resultsWNT-3A increased the levels of NRF2 and its transcriptional signature in mouse hepatocytes and HEK293T cells. The use of short interfering RNAs in hepatocytes and mouse embryonic fibroblasts which are deficient in the redox sensor Kelch-like ECH-associated protein 1 (KEAP1) indicated that WNT-3A activates NRF2 in a β-Catenin- and KEAP1-independent manner. WNT-3A stabilized NRF2 by preventing its GSK-3-dependent phosphorylation and subsequent SCF/β-TrCP-dependent ubiquitination and proteasomal degradation. Axin1 and NRF2 were physically associated in a protein complex that was regulated by WNT-3A, involving the central region of Axin1 and the Neh4/Neh5 domains of NRF2. Axin1 knockdown increased NRF2 protein levels, while Axin1 stabilization with Tankyrase inhibitors blocked WNT/NRF2 signaling. The relevance of this novel pathway was assessed in mice with a conditional deletion of Axin1 in the liver, which showed upregulation of the NRF2 signature in hepatocytes and disruption of liver zonation of antioxidant metabolism. INNOVATION: NRF2 takes part in a protein complex with Axin1 that is regulated by the canonical WNT pathway. This new WNT-NRF2 axis controls the antioxidant metabolism of hepatocytes.
conclusionThese results uncover the participation of NRF2 in a WNT-regulated signalosome that participates in basal maintenance of hepatic antioxidant metabolism.
Indexed as
Identifiers
What OpenQuestion holds
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.