ArticleHepatology (Baltimore, Md.)2019
Dysregulated Autophagy and Lysosome Function Are Linked to Exosome Production by Micro-RNA 155 in Alcoholic Liver Disease.
Article in Hepatology (Baltimore, Md.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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Who cites it
117 citing papers in PubMed, 213 citations in OpenAlex.
- CD147 promotes NSCLC metastasis by inducing secretory autophagy-dependent exosome secretion via TRIM56-mediated ubiquitination and degradation of GCN2.Cell death and differentiation · 2026Article
- Liver-nervous system axis: pathways, dysregulation, and translational perspectives.Journal of neuroinflammation · 2026Review
- Ubiquilin 1 Inhibits intracellular proliferation of Salmonella enterica serovar Typhimurium through Xenophagy.Genes & genomics · 2026Article
- mTOR-driven integrin β4-enriched extracellular vesicles from lenvatinib-resistant hepatocellular carcinoma fuel lung metastasis via fibroblast-niche formation.Signal transduction and targeted therapy · 2026Article
- Cyclic GMP-AMP synthase deficiency predisposes the liver to alcohol-induced cell death and ER stress.Hepatology communications · 2026Article
- Roles of Extracellular Vesicle-Derived microRNAs in Metabolic Dysfunction-Associated Steatotic Liver Disease to Hepatocellular Carcinoma.Biomedicines · 2026Review
- MiR-18a-5p Attenuates Oxidative Stress and Inhibits Lipid Accumulation in Alcoholic Fatty Liver by Activating the CYP1A1-PPAR Axis.Immunity, inflammation and disease · 2026Article
- Article
- The role of mitochondrial DNA and RNA in promoting liver disease pathogenesis.Frontiers in cell and developmental biology · 2026Review
- Autophagy in the liver.Autophagy reports · 2026Review
- The impact of obesity on bone health: molecular pathways, metabolic interactions, and associated pathologies.International journal of obesity (2005) · 2026Review
- Autophagy activation within inflammatory microenvironment improved the therapeutic effect of MSC-Derived extracellular Vesicle in SLE.Journal of advanced research · 2025Article
- The efficacy of rosuvastatin to reduce circulating tissue factor extracellular vesicles after ovarian cancer surgery.Blood advances · 2025Article
- Overexpression miR-125a-5p inhibits HSCs activation and alleviates liver fibrosis through TGF-β/Smad2/3 signaling pathway and autophagy.Cell death discovery · 2025Article
- mTOR Signaling in Macrophages: All Depends on the Context.International journal of molecular sciences · 2025Review
- Reprogramming of hsa_circ_0008719 and its target miR-3615 induced by TOB1 in exosomes of gastric cancer cells: a contribution to inhibit gastric cancer progression.Scientific reports · 2025Article
- ROS Regulate Rotenone-induced SH-SY5Y Dopamine Neuron Death Through Ferroptosis-mediated Autophagy and Apoptosis.Molecular neurobiology · 2025Article
- Extracellular Vesicles as Biomarkers in Chronic Hepatobiliary Diseases: An Overview of Their Interplay.International journal of molecular sciences · 2025Review
- The role of gut microbiota, exosomes, and their interaction in the pathogenesis of ALD.Journal of advanced research · 2025Review
- Extracellular Vesicles and Micro-RNAs in Liver Disease.Seminars in liver disease · 2025Review
57 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Cellular homeostais, that is normally maintained through autophagy, is disrupted in alcoholic liver disease (ALD). Because autophagy and exosome biogenesis share common elements, we hypothesized that increased exosome production in ALD may be linked to disruption of autophagic function. We found impaired autophagy both in ALD and alcoholic hepatitis (AH) mouse models and human livers with ALD as indicated by increased hepatic p62 and LC3-II levels. Alcohol reduced autophagy flux in vivo in chloroquine-treated mice as well as in vitro in hepatocytes and macrophages treated with bafilomycin A. Our results revealed that alcohol targets multiple steps in the autophagy pathway. Alcohol-related decrease in mechanistic target of rapamycin (mTOR) and Ras homolog enriched in brain (Rheb), that initiate autophagy, correlated with increased Beclin1 and autophagy-related protein 7 (Atg7), proteins involved in phagophore-autophagosome formation, in ALD. We found that alcohol disrupted autophagy function at the lysosomal level through decreased lysosomal-associated membrane protein 1 (LAMP1) and lysosomal-associated membrane protein 2 (LAMP2) in livers with ALD. We identified that micro-RNA 155 (miR-155), that is increased by alcohol, targets mTOR, Rheb, LAMP1, and LAMP2 in the authophagy pathway. Consistent with this, miR-155-deficient mice were protected from alcohol-induced disruption of autophagy and showed attenuated exosome production. Mechanistically, down-regulation of LAMP1 or LAMP2 increased exosome release in hepatocytes and macrophages in the presence and absence of alcohol. These results suggested that the alcohol-induced increase in exosome production was linked to disruption of autophagy and impaired autophagosome and lysosome function. Conclusion: Alcohol affects multiple genes in the autophagy pathway and impairs autophagic flux at the lysosome level in ALD. Inhibition of LAMP1 and LAMP2 promotes exosome release in ALD. We identified miR-155 as a mediator of alcohol-related regulation of autophagy and exosome production in hepatocytes and macrophages.
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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.