ArticleCellular and molecular gastroenterology and hepatology2018
Demethylase JMJD6 as a New Regulator of Interferon Signaling: Effects of HCV and Ethanol Metabolism.
Article in Cellular and molecular gastroenterology and hepatology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Ethanol Disrupts the Protective Crosstalk Between Macrophages and HBV-Infected Hepatocytes.Biomolecules · 2025Article
- The long non-coding RNA lncRNA-DRNR enhances infectious bronchitis virus replication by targeting chicken JMJD6 and modulating interferon-stimulated genes expression via the JAK-STAT signalling pathway.Veterinary research · 2024Article
- Alcohol-Associated Liver Disease Outcomes: Critical Mechanisms of Liver Injury Progression.Biomolecules · 2024Review
- Immunological pathways in viral hepatitis-induced hepato-cellular carcinoma.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- Post-translational modifications of histone and non-histone proteins in epigenetic regulation and translational applications in alcohol-associated liver disease: Challenges and research opportunities.Pharmacology & therapeutics · 2023Review
- JMJD6 functions as an oncogene and is associated with poor prognosis in esophageal squamous cell carcinoma.BMC cancer · 2023Article
- A specific JMJD6 inhibitor potently suppresses multiple types of cancers both in vitro and in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Beneficial Effects of Betaine: A Comprehensive Review.Biology · 2021Review
- JMJD6 negatively regulates cytosolic RNA induced antiviral signaling by recruiting RNF5 to promote activated IRF3 K48 ubiquitination.PLoS pathogens · 2021Article
- Second hits exacerbate alcohol-related organ damage: an update.Alcohol and alcoholism (Oxford, Oxfordshire) · 2021Review
- Obeticholic acid attenuates human immunodeficiency virus/alcohol metabolism-induced pro-fibrotic activation in liver cells.World journal of hepatology · 2020Article
- Acetaldehyde suppresses HBV-MHC class I complex presentation on hepatocytes via induction of ER stress and Golgi fragmentation.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Jumonji domain-containing protein 6 protein and its role in cancer.Cell proliferation · 2020Review
- Alcohol Metabolism Potentiates HIV-Induced Hepatotoxicity: Contribution to End-Stage Liver Disease.Biomolecules · 2019Article
- Acetaldehyde suppresses the display of HBV-MHC class I complexes on HBV-expressing hepatocytes.American journal of physiology. Gastrointestinal and liver physiology · 2019Article
- Hepatocyte PRMT1 protects from alcohol induced liver injury by modulating oxidative stress responses.Scientific reports · 2019Article
- The small members of the JMJD protein family: Enzymatic jewels or jinxes?Biochimica et biophysica acta. Reviews on cancer · 2019Review
- Article
- Human hepatocyte depletion in the presence of HIV-1 infection in dual reconstituted humanized mice.Biology open · 2018Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsAlcohol-induced progression of hepatitis C virus (HCV) infection is related to dysfunction of innate immunity in hepatocytes. Endogenously produced interferon (IFN)α induces activation of interferon-stimulated genes (ISGs) via triggering of the Janus kinase-signal transducer and activator of transcription 1 (STAT1) pathway. This activation requires protein methyltransferase 1-regulated arginine methylation of STAT1. Here, we aimed to study whether STAT1 methylation also depended on the levels of demethylase jumonji domain-containing 6 protein (JMJD6) and whether ethanol and HCV affect JMJD6 expression in hepatocytes.
methodsHuh7.5-CYP (RLW) cells and hepatocytes were exposed to acetaldehyde-generating system (AGS) and 50 mmol/L ethanol, respectively. JMJD6 messenger RNA and protein expression were measured by real-time polymerase chain reaction and Western blot. IFNα-activated cells either overexpressing JMJD6 or with knocked-down JMJD6 expression were tested for STAT1 methylation, ISG activation, and HCV RNA. In vivo studies have been performed on C57Bl/6 mice (expressing HCV structural proteins or not) or chimeric mice with humanized livers fed control or ethanol diets.
resultsAGS exposure to cells up-regulated JMJD6 expression in RLW cells. These results were corroborated by ethanol treatment of primary hepatocytes. The promethylating agent betaine reversed the effects of AGS/ethanol. Similar results were obtained in vivo, when mice were fed control/ethanol with and without betaine supplementation. Overexpression of JMJD6 suppressed STAT1 methylation, IFNα-induced ISG activation, and increased HCV-RNA levels. In contrast, JMJD6 silencing enhanced STAT1 methylation, ISG stimulation by IFNα, and attenuated HCV-RNA expression in Huh7.5 cells.
conclusionsWe conclude that arginine methylation of STAT1 is suppressed by JMJD6. Both HCV and acetaldehyde increase JMJD6 levels, thereby impairing STAT1 methylation and innate immunity protection in hepatocytes exposed to the virus and/or alcohol.
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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.