ArticleScientific reports2017
Protection against oxidative stress mediated by the Nrf2/Keap1 axis is impaired in Primary Biliary Cholangitis.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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55 citing papers in PubMed, 98 citations in OpenAlex.
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- Machine Learning Predicts Treatment Response and Prognostic Pathways From Whole-Blood Transcriptome in Primary Biliary Cholangitis.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Primary Biliary Cholangitis Pathogenesis: A Pathophysiology-Based Narrative Review.International journal of molecular sciences · 2026Review
- Modulation of Nrf2 and Mitochondrial Function: Pharmacological Implications.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Ferroptosis in Diabetic Cardiomyopathy and Atherosclerosis: Mechanisms and Clinical Prospects.International journal of molecular sciences · 2025Review
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- Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases.Redox biology · 2025Review
- Using transcriptomic signatures to elucidate individual and mixture effects of inorganic arsenic and manganese in human placental trophoblast HTR-8/SVneo cells.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Role of Nrf2 in Oxidative Stress, Neuroinflammation and Autophagy in Alzheimer's Disease: Regulation of Nrf2 by Different Signaling Pathways.Current molecular medicine · 2025Review
- Secretome of human amniotic membrane stem cells promote recovery and testicular functions through modulatingInternational journal of reproductive biomedicine · 2024Article
- Digital manufacturing techniques and the in vitro biocompatibility of acrylic-based occlusal device materials.Clinical oral investigations · 2024Article
- KEAP1 overexpression is correlated with poor prognosis and immune infiltration in liver hepatocellular carcinoma.Frontiers in medicine · 2024Article
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- Keap1-Nrf2 pathway: a key mechanism in the occurrence and development of cancer.Frontiers in oncology · 2024Review
- MicroRNAs participate in the regulation of apoptosis and oxidative stress-related gene expression in rabbits infected withFrontiers in microbiology · 2024Article
- Regulation of Keap1-Nrf2 axis in temporal lobe epilepsy-hippocampal sclerosis patients may limit the seizure outcomes.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Article
- Age and oxidative stress regulate Nrf2 homeostasis in human articular chondrocytes.Osteoarthritis and cartilage · 2023Article
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- Moderate exercise-induced dynamics on key sepsis-associated signaling pathways in the liver.Critical care (London, England) · 2023Article
- RGFP966 exerts neuroprotective effect via HDAC3/Nrf2 pathway after surgical brain injury in rats.Heliyon · 2023Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In response to oxidative stress, nuclear factor (erythroid-derived 2)-like2 (Nrf2) induces expression of cytoprotective genes. The Nrf2 pathway is controlled by microRNAs and Kelch-like ECH-associated protein1 (Keap1). Nrf2 is stabilized when Keap1 is degraded through the autophagy pathway in a p62-dependent manner. The inhibition of autophagy causes protein accumulation, and Keap1 is inactivated by binding to p62. We investigated the role of the Nrf2/Keap1 axis in the amelioration of oxidative stress in primary biliary cholangitis (PBC). Liver specimens from patients with PBC, with (n = 24) or without cirrhosis (n = 14), and from controls (n = 16) were used for molecular analyses. We found that Nrf2 protein levels were elevated in PBC compared to controls, but Nrf2 gene expression was significantly reduced in cirrhotic PBC. Nrf2 target gene products, HO-1 and GCLC proteins, were reduced compared to controls and reduction of Nrf2 gene expression was associated with elevated levels of microRNA-132 and microRNA-34a. Both Keap1 and p62 protein levels were substantially increased in PBC compared to controls. PBC was associated with reduced Nrf2 expression and autophagy deterioration and these impairments were more advanced in patients with cirrhosis. Aberrant Nrf2/Keap1 system integrity may affect self-defence mechanisms against oxidative stress in PBC.
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