ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2013
Purinergic receptor X7 is a key modulator of metabolic oxidative stress-mediated autophagy and inflammation in experimental nonalcoholic steatohepatitis.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 62 citations in OpenAlex.
- Liver Fibrosis and Purinergic Signaling: Autocrine-Paracrine Role of ATP in Liver Damage.International journal of molecular sciences · 2026Review
- Neutrophil-T cell cross talk in noninfectious liver diseases.American journal of physiology. Gastrointestinal and liver physiology · 2026Review
- Bibliometric Analysis of Emerging Trends and Hotspots in the Links between Nonalcoholic Steatohepatitis and Diabetes Mellitus from 2004 to 2023.Endocrine, metabolic & immune disorders drug targets · 2026Review
- Chaperone-Mediated Autophagy Reactivation Protects Against Severe Acute Pancreatitis-Associated Liver Injury Through Upregulating Keap1/Nrf2 Signaling Pathway and Inhibiting NLRP3 Inflammasome Activation.Cell biochemistry and biophysics · 2025Article
- Retinal Pigment Epithelium Under Oxidative Stress: Chaperoning Autophagy and Beyond.International journal of molecular sciences · 2025Review
- Purinergic signaling and cholangiocyte regeneration: a new frontier in ischemic liver injury.Frontiers in transplantation · 2025Review
- Lipophagy and epigenetic alterations are related to metabolic dysfunction-associated steatotic liver disease progression in an experimental model.World journal of hepatology · 2024Article
- Purinergic Signaling in Non-Parenchymal Liver Cells.International journal of molecular sciences · 2024Review
- Involvement of Lipophagy and Chaperone-Mediated Autophagy in the Pathogenesis of Non-Alcoholic Fatty Liver Disease by Regulation of Lipid Droplets.International journal of molecular sciences · 2023Review
- Knockout of Purinergic P2YInternational journal of molecular sciences · 2023Article
- Role of purinergic signalling in obesity-associated end-organ damage: focus on the effects of natural plant extracts.Frontiers in endocrinology · 2023Review
- Caffeine and Its Antioxidant Properties-It Is All about Dose and Source.International journal of molecular sciences · 2022Review
- Role of CaInternational journal of molecular medicine · 2022Review
- The P2X7R-NLRP3 and AIM2 Inflammasome Platforms Mark the Complexity/Severity of Viral or Metabolic Liver Damage.International journal of molecular sciences · 2022Article
- Role of the Inflammasome in Liver Disease.Annual review of pathology · 2022Review
- Chaperone-mediated autophagy and disease: Implications for cancer and neurodegeneration.Molecular aspects of medicine · 2021Article
- Dysfunction of chaperone-mediated autophagy in human diseases.Molecular and cellular biochemistry · 2021Review
- Purinergic Signaling in Liver Pathophysiology.Frontiers in endocrinology · 2021Review
- The Dual Role of Autophagy in Cancer Development and a Therapeutic Strategy for Cancer by Targeting Autophagy.International journal of molecular sciences · 2020Review
- Purinergic signalling in liver diseases: Pathological functions and therapeutic opportunities.JHEP reports : innovation in hepatology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Recent studies indicate that metabolic oxidative stress, autophagy, and inflammation are hallmarks of nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanisms that link these important events in NASH remain unclear. In this study, we investigated the mechanistic role of purinergic receptor X7 (P2X7) in modulating autophagy and resultant inflammation in NASH in response to metabolic oxidative stress. The study uses two rodent models of NASH. In one of them, a CYP2E1 substrate bromodichloromethane is used to induce metabolic oxidative stress and NASH. Methyl choline-deficient diet feeding is used for the other NASH model. CYP2E1 and P2X7 receptor gene-deleted mice are used to establish their roles in regulating metabolic oxidative stress and autophagy. Autophagy gene expression, protein levels, confocal microscopy based-immunolocalization of lysosome-associated membrane protein (LAMP)2A and histopathological analysis were performed. CYP2E1-dependent metabolic oxidative stress induced increases in P2X7 receptor expression and chaperone-mediated autophagy markers LAMP2A and heat shock cognate 70 but caused depletion of light chain 3 isoform B (LC3B) protein levels. P2X7 receptor gene deletion significantly decreased LAMP2A and inflammatory indicators while significantly increasing LC3B protein levels compared with wild-type mice treated with bromodichloromethane. P2X7 receptor-deleted mice were also protected from NASH pathology as evidenced by decreased inflammation and fibrosis. Our studies establish that P2X7 receptor is a key regulator of autophagy induced by metabolic oxidative stress in NASH, thereby modulating hepatic inflammation. Furthermore, our findings presented here form a basis for P2X7 receptor as a potential therapeutic target in the treatment for NASH.
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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.