ArticleHepatology (Baltimore, Md.)2016
Retinoid regulation of antiviral innate immunity in hepatocytes.
Article in Hepatology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 30 citations in OpenAlex.
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- N-Acetyl Cysteine Restores the Diminished Activity of the Antioxidant Enzymatic System Caused by SARS-CoV-2 Infection: Preliminary Findings.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Long-term cell fate and functional maintenance of human hepatocyte through stepwise culture configuration.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Role of ALDH2 in Hepatic Disorders: Gene Polymorphism and Disease Pathogenesis.Journal of clinical and translational hepatology · 2021Review
- Art of Making Artificial Liver: Depicting Human Liver Biology and Diseases in Mice.Seminars in liver disease · 2020Review
- Seasonal Variability and Shared Molecular Signatures of Inactivated Influenza Vaccination in Young and Older Adults.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Aldehyde Dehydrogenase, Liver Disease and Cancer.International journal of biological sciences · 2020Review
- Regulation of Hepatitis C Virus Infection by Cellular Retinoic Acid Binding Proteins through the Modulation of Lipid Droplet Abundance.Journal of virology · 2019Article
- The putative tumour suppressor protein Latexin is secreted by prostate luminal cells and is downregulated in malignancy.Scientific reports · 2019Article
- Identification of Retinoic Acid Receptor Agonists as Potent Hepatitis B Virus Inhibitors via a Drug Repurposing Screen.Antimicrobial agents and chemotherapy · 2018Article
- Dietary and metabolic modulators of hepatic immunity.Seminars in immunopathology · 2018Review
- Demethylase JMJD6 as a New Regulator of Interferon Signaling: Effects of HCV and Ethanol Metabolism.Cellular and molecular gastroenterology and hepatology · 2018Article
- Dual modulation of human hepatic zonation via canonical and non-canonical Wnt pathways.Experimental & molecular medicine · 2017Article
- Transcriptional Regulation of Antiviral Interferon-Stimulated Genes.Trends in microbiology · 2017Review
- Organ system view of the hepatic innate immunity in HCV infection.Journal of medical virology · 2016Review
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9 authors at 5 institutions in 2 countries.
Funding
Abstract
unlabelledPersistent infection of hepatitis C virus (HCV) is one of the leading causes of end-stage liver disease (ESLD), such as decompensated cirrhosis and liver cancer. Of particular note, nearly half of HCV-infected people in the United States are reported to be heavy drinkers. This particular group of patients is known to rapidly progress to the ESLD. Although accelerated disease progression among alcohol abusers infected with HCV is clinically well recognized, the molecular pathophysiology behind this manifestation has not been well elucidated. Hepatocytes metabolize ethanol (EtOH) primarily through two steps of oxidative catabolism in which alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) play central roles. The ADH-ALDH pathway also governs the metabolism of retinol (vitamin A) to its transcriptionally active metabolite, retinoic acid (RA). In this study, we defined that the ADH-ALDH pathway serves as a potent antiviral host factor in hepatocytes, which regulates the expression of interferon (IFN)-stimulated genes (ISGs) by biogenesis of RA. ISGs constitute over 300 antiviral effectors, which cooperatively govern intracellular antiviral innate immunity. Our study revealed that intracellular RA levels greatly influence ISG expression under basal conditions. Moreover, RA augments ISG induction in response to viral infection or exposure to IFN in a gene-specific manner. Lastly, our results demonstrated that EtOH attenuates the antiviral function of the ADH-ALDH pathway, which suggests the possibility that EtOH-retinol metabolic competition is one of the molecular mechanisms for the synergism between HCV and alcohol abuse in liver disease progression.
conclusionsRA plays a critical role in the regulation of intracellular antiviral innate immunity in hepatocytes. (Hepatology 2016;63:1783-1795).
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