ArticleMolecular and cellular biology2014
Nrf2 enhances cholangiocyte expansion in Pten-deficient livers.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 97 citations in OpenAlex.
- Targeting Hippocampal PTEN Suppresses Ferroptosis and Rescues Cognitive Decline in Alzheimer's Disease via Dual AKT/GSK3β/Nrf2 and AKT/STAT3 Axes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Interplay between NRF2 post-translational modifications and protein-protein interactions: Perspectives from emerging structural and functional evidence.Archives of biochemistry and biophysics · 2026Review
- A novel β-TrCP1/NRF2 interaction inhibitor for effective anti-inflammatory therapy.Journal of biomedical science · 2025Article
- Review
- Study on the mechanism of hepatotoxicity of Aucklandiae radix through liver metabolomics and network pharmacology.Toxicology research · 2024Article
- Hepatic malonyl-CoA synthesis restrains gluconeogenesis by suppressing fat oxidation, pyruvate carboxylation, and amino acid availability.Cell metabolism · 2024Article
- The nuclear factor erythroid 2-related factor 2/p53 axis in breast cancer.Biochemia medica · 2023Review
- Advances in Understanding the Role of NRF2 in Liver Pathophysiology and Its Relationship with Hepatic-Specific Cyclooxygenase-2 Expression.Antioxidants (Basel, Switzerland) · 2023Review
- Identification of NRF2 Activation as a Prognostic Biomarker in T-Cell Acute Lymphoblastic Leukaemia.International journal of molecular sciences · 2023Article
- NRF2 and the Moirai: Life and Death Decisions on Cell Fates.Antioxidants & redox signaling · 2023Review
- MicroRNA-21 and microRNA-148a affects PTEN, NO and ROS in canine leishmaniasis.Frontiers in genetics · 2023Article
- Exosomes Derived from BMSCs Ameliorate Intestinal Ischemia-Reperfusion Injury by Regulating miR-144-3p-Mediated Oxidative Stress.Digestive diseases and sciences · 2022Article
- The KEAP1-NRF2 System and Esophageal Cancer.Cancers · 2022Review
- The β-TrCP-Mediated Pathway Cooperates with the Keap1-Mediated Pathway in Nrf2 DegradationMolecular and cellular biology · 2022Article
- Article
- Nrf2 attenuates hyperglycemia-induced nNOS impairment in adult mouse primary enteric neuronal crest cells and normalizes stomach function.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- FOXO1 regulates pentose phosphate pathway-mediated induction of developmental erythropoiesis.Frontiers in cell and developmental biology · 2022Article
- Nrf2 deficiency causes hepatocyte dedifferentiation and reduced albumin production in an experimental extrahepatic cholestasis model.PloS one · 2022Article
- Tocotrienols reach the brain and play roles in the attenuation of body weight gain and improvement of cognitive function in high-fat diet-treated mice.Journal of clinical biochemistry and nutrition · 2021Article
- A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling.Nature communications · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Keap1-Nrf2 system plays a central role in the stress response. While Keap1 ubiquitinates Nrf2 for degradation under unstressed conditions, this Keap1 activity is abrogated in response to oxidative or electrophilic stresses, leading to Nrf2 stabilization and coordinated activation of cytoprotective genes. We recently found that nuclear accumulation of Nrf2 is significantly increased by simultaneous deletion of Pten and Keap1, resulting in the stronger activation of Nrf2 target genes. To clarify the impact of the cross talk between the Keap1-Nrf2 and Pten-phosphatidylinositide 3-kinase-Akt pathways on the liver pathophysiology, in this study we have conducted closer analysis of liver-specific Pten::Keap1 double-mutant mice (Pten::Keap1-Alb mice). The Pten::Keap1-Alb mice were lethal by 1 month after birth and displayed severe hepatomegaly with abnormal expansion of ductal structures comprising cholangiocytes in a Nrf2-dependent manner. Long-term observation of Pten::Keap1-Alb::Nrf2(+/-) mice revealed that the Nrf2-heterozygous mice survived beyond 1 month but developed polycystic liver fibrosis by 6 months. Gsk3 directing the Keap1-independent degradation of Nrf2 was heavily phosphorylated and consequently inactivated by the double deletion of Pten and Keap1 genes. Thus, liver-specific disruption of Keap1 and Pten augments Nrf2 activity through inactivation of Keap1-dependent and -independent degradation of Nrf2 and establishes the Nrf2-dependent molecular network promoting the hepatomegaly and cholangiocyte expansion.
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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.