ArticleJCI insight2020
Chronic-plus-binge alcohol intake induces production of proinflammatory mtDNA-enriched extracellular vesicles and steatohepatitis via ASK1/p38MAPKα-dependent mechanisms.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Neutrophil extracellular traps (NETs) and NETosis in alcohol-associated diseases: A systematic review.Alcohol, clinical & experimental research · 2025Pooled it
- TRAIP Mediates Alcohol-Induced Liver Injury through Regulating β-catenin Ubiquitin Degradation via Direct Interaction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- P2X7R Signaling and Differential Regulation of Neuroinflammatory and Behavior Responses in Male and Female Mice During Chronic Ethanol Exposure.International journal of molecular sciences · 2026Article
- Therapeutic and diagnostic potential of extracellular vesicle (EV)-mediated intercellular transfer of mitochondria and mitochondrial components.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- The role of circulating metallothionein 1 in voriconazole-associated hepatotoxicity.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Spatial immune niche remodeling of the neutrophil-macrophage axis inchronic liver disease.Frontiers in cell and developmental biology · 2026Review
- The role of mitochondrial DNA and RNA in promoting liver disease pathogenesis.Frontiers in cell and developmental biology · 2026Review
- Gut microbiota-mitochondria-barrier-multiorgan axis: a network-based hypothesis for systemic injury.Frontiers in immunology · 2026Review
- Purinergic and extracellular vesicle signaling in alcohol-induced blood-brain barrier breakdown and neuroimmune activation.Brain, behavior, and immunity · 2025Review
- Metallothioneins in the Pathogenesis of Liver Diseases: A Review.International journal of hepatology · 2025Review
- Alcohol-Associated Hepatitis: Translating Pathophysiology into Targeted Clinical Trials.Current hepatology reports · 2025Review
- Extracellular vesicles: opening up a new perspective for the diagnosis and treatment of mitochondrial dysfunction.Journal of nanobiotechnology · 2024Review
- Metallothionein: A Comprehensive Review of Its Classification, Structure, Biological Functions, and Applications.Antioxidants (Basel, Switzerland) · 2024Review
- Oxidative stress induces extracellular vesicle release by upregulation of HEXB to facilitate tumour growth in experimental hepatocellular carcinoma.Journal of extracellular vesicles · 2024Article
- The micro-743a-3p-GSTM1 pathway is an endogenous protective mechanism against alcohol-related liver disease in mice.Cellular & molecular biology letters · 2024Article
- Hepatic TRPC3 loss contributes to chronic alcohol consumption-induced hepatic steatosis and liver injury in mice.Life metabolism · 2024Article
- The Dynamic Role of Endoplasmic Reticulum Stress in Chronic Liver Disease.The American journal of pathology · 2023Review
- Small-molecule chemical probes for the potential therapeutic targets in alcoholic liver diseases.Liver research (Beijing, China) · 2023Review
- New insights in the pathogenesis of alcohol-related liver disease: The metabolic, immunologic, and neurologic pathwaysLiver research (Beijing, China) · 2023Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Alcohol-associated liver disease is a spectrum of liver disorders with histopathological changes ranging from simple steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Recent data suggest that chronic-plus-binge ethanol intake induces steatohepatitis by promoting release by hepatocytes of proinflammatory mitochondrial DNA-enriched (mtDNA-enriched) extracellular vesicles (EVs). The aim of the present study was to investigate the role of the stress kinase apoptosis signal-regulating kinase 1 (ASK1) and p38 mitogen-activated protein kinase (p38) in chronic-plus-binge ethanol-induced steatohepatitis and mtDNA-enriched EV release. Microarray analysis revealed the greatest hepatic upregulation of metallothionein 1 and 2 (Mt1/2), which encode 2 of the most potent antioxidant proteins. Genetic deletion of the Mt1 and Mt2 genes aggravated ethanol-induced liver injury, as evidenced by elevation of serum ALT, neutrophil infiltration, oxidative stress, and ASK1/p38 activation in the liver. Inhibition or genetic deletion of Ask1 or p38 ameliorated ethanol-induced liver injury, inflammation, ROS levels, and expression of phagocytic oxidase and ER stress markers in the liver. In addition, inhibition of ASK1 or p38 also attenuated ethanol-induced mtDNA-enriched EV secretion from hepatocytes. Taken together, these findings indicate that induction of hepatic mtDNA-enriched EVs by ethanol is dependent on ASK1 and p38, thereby promoting alcoholic steatohepatitis.
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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.