ArticleThe American journal of pathology2013
Hepatitis C and alcohol exacerbate liver injury by suppression of FOXO3.
Article in The American journal of pathology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Simultaneous binding of quercetin and catechin to FOXO3 enhances IKKα transcription inhibition and suppression of oxidative stress-induced acute alcoholic liver injury in rats.Journal of advanced research · 2025Article
- Protein arginine methylation in viral infection and antiviral immunity.International journal of biological sciences · 2023Review
- CYP2E1-dependent upregulation of SIRT7 is response to alcohol mediated metastasis in hepatocellular carcinoma.Cancer gene therapy · 2022Article
- FoxO3 Modulates LPS-Activated Hepatic Inflammation in Turbot (Frontiers in immunology · 2021Article
- Hepatitis C Prevalence and Management Among Patients Receiving Opioid Substitution Treatment in General Practice in Ireland: Baseline Data from a Feasibility Study.Interactive journal of medical research · 2018Article
- FOXO3-dependent apoptosis limits alcohol-induced liver inflammation by promoting infiltrating macrophage differentiation.Cell death discovery · 2018Article
- Alcohol exposure differentially effects anti-tumor immunity in females by altering dendritic cell function.Alcohol (Fayetteville, N.Y.) · 2016Article
- Pathogenesis of Alcoholic Liver Disease.Clinics in liver disease · 2016Review
- Serine 574 phosphorylation alters transcriptional programming of FOXO3 by selectively enhancing apoptotic gene expression.Cell death and differentiation · 2016Article
- High-throughput sequencing reveals altered expression of hepatic microRNAs in nonalcoholic fatty liver disease-related fibrosis.Translational research : the journal of laboratory and clinical medicine · 2015Article
- Role of farnesoid X receptor and bile acids in alcoholic liver disease.Acta pharmaceutica Sinica. B · 2015Review
- New advances in molecular mechanisms and emerging therapeutic targets in alcoholic liver diseases.World journal of gastroenterology · 2014Review
- Alcoholic hepatitis and concomitant hepatitis C virus infection.World journal of gastroenterology · 2014Review
- Oncogenic signaling pathways and origins of tumor-initiating stem-like cells of hepatocellular carcinomas induced by hepatitis C virus, alcohol and/or obesity.Hepatology international · 2014Article
- Role of hypoxia inducing factor-1β in alcohol-induced autophagy, steatosis and liver injury in mice.PloS one · 2014Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Hepatitis C virus (HCV) infection exacerbates alcoholic liver injury by mechanisms that include enhanced oxidative stress. The forkhead box transcription factor FOXO3 is an important component of the antioxidant stress response that can be altered by HCV. To test whether FOXO3 is protective for alcoholic liver injury, we fed alcohol to FOXO3(-/-) mice. After 3 weeks, one third of these mice developed severe hepatic steatosis, neutrophilic infiltration, and >10-fold alanine aminotransferase (ALT) elevations. In cell culture, either alcohol or HCV infection alone increased FOXO3 transcriptional activity and expression of target genes, but the combination of HCV and alcohol together caused loss of nuclear FOXO3 and decreased its transcriptional activity. This was accompanied by increased phosphorylation of FOXO3. Mice expressing HCV structural proteins on a background of reduced expression of superoxide dismutase 2 (SOD2; Sod2(+/-)) also had increased liver sensitivity to alcohol, with elevated ALT, steatosis, and lobular inflammation. Elevated ALT was associated with an alcohol-induced decrease in SOD2 and redistribution of FOXO3 to the cytosol. These results demonstrate that FOXO3 functions as a protective factor preventing alcoholic liver injury. The combination of HCV and alcohol, but not either condition alone, inactivates FOXO3, causing a decrease in expression of its target genes and an increase in liver injury. Modulation of the FOXO3 pathway is a potential therapeutic approach for HCV-alcohol-induced liver injury.
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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.