ArticleJournal of hepatology2015
Alcohol directly stimulates epigenetic modifications in hepatic stellate cells.
Article in Journal of hepatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
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The trial behind it
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Who cites it
56 citing papers in PubMed, 97 citations in OpenAlex.
- Liver Injury and Endotoxemia in Male and Female Alcohol-Dependent Individuals Admitted to an Alcohol Treatment Program.Alcoholism, clinical and experimental research · 2017Trial
- Ethanol reshapes FFC-driven steatohepatitis through time-dependent fibrosis and lipid-droplet remodeling.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Pulpitis Transiently Affect Hepatic Bone Morphogenetic Protein 9 Expression by Lipopolysaccharide.International dental journal · 2026Article
- Single cell multiomic landscape reveals gene programs driving lipid droplet heterogeneity in hepatic steatosis.Scientific reports · 2026Article
- Article
- The Sugar-Coated Truth of Alcohol-Associated Liver Disease: Galectins as Multifaceted Regulators of Alcohol-Induced Liver Injury.The American journal of pathology · 2026Review
- Unraveling the pleiotropic effects of CCR2-dependent signal transduction in fibrosis development.Theranostics · 2026Review
- Hepatic stellate cells in liver fibrosis: From biology to pathology.Open veterinary journal · 2025Review
- Sodium butyrate attenuates liver fibrogenesis via promoting H4K8 crotonylation.Molecular and cellular biochemistry · 2025Article
- Long Non-Coding RNAs in Non-Alcoholic Fatty Liver Disease; Friends or Foes?Cell biochemistry and biophysics · 2025Review
- Histone methyltransferase KMT2A promotes pulmonary fibrogenesis via targeting pro-fibrotic factor PU.1 in fibroblasts.Clinical and translational medicine · 2025Article
- ASH1L in Hepatoma Cells and Hepatic Stellate Cells Promotes Fibrosis-Associated Hepatocellular Carcinoma by Modulating Tumor-Associated Macrophages.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Fibroblast and myofibroblast activation in normal tissue repair and fibrosis.Nature reviews. Molecular cell biology · 2024Review
- Development of an alcoholic liver disease model for drug evaluation from human induced pluripotent stem cell-derived liver organoids.Acta biochimica et biophysica Sinica · 2024Article
- Alcohol-Associated Liver Disease Outcomes: Critical Mechanisms of Liver Injury Progression.Biomolecules · 2024Review
- Linking fatty liver diseases to hepatocellular carcinoma by hepatic stellate cells.Journal of the National Cancer Center · 2024Review
- Non-canonical MLL1 activity regulates centromeric phase separation and genome stability.Nature cell biology · 2023Article
- Alterations in the hepatocyte epigenetic landscape in steatosis.Epigenetics & chromatin · 2023Article
- Unraveling the Complex Interplay between Epigenetics and Immunity in Alcohol-Associated Liver Disease: A ComprehensiveInternational journal of biological sciences · 2023Review
- Advances in DNA, histone, and RNA methylation mechanisms in the pathophysiology of alcohol use disorder.Advances in drug and alcohol research · 2023Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsAlcohol is a primary cause of liver disease and an important co-morbidity factor in other causes of liver disease. A common feature of progressive liver disease is fibrosis, which results from the net deposition of fibril-forming extracellular matrix (ECM). The hepatic stellate cell (HSC) is widely considered to be the major cellular source of fibrotic ECM. We determined if HSCs are responsive to direct stimulation by alcohol.
methodsHSCs undergoing transdifferentiation were incubated with ethanol and expression of fibrogenic genes and epigenetic regulators was measured. Mechanisms responsible for recorded changes were investigated using ChIP-Seq and bioinformatics analysis. Ethanol induced changes were confirmed using HSCs isolated from a mouse alcohol model and from ALD patient's liver and through precision cut liver slices.
resultsHSCs responded to ethanol exposure by increasing profibrogenic and ECM gene expression including elastin. Ethanol induced an altered expression of multiple epigenetic regulators, indicative of a potential to modulate chromatin structure during HSC transdifferentiation. MLL1, a histone 3 lysine 4 (H3K4) methyltransferase, was induced by ethanol and recruited to the elastin gene promoter where it was associated with enriched H3K4me3, a mark of active chromatin. Chromatin immunoprecipitation sequencing (ChIPseq) revealed that ethanol has broad effects on the HSC epigenome and identified 41 gene loci at which both MML1 and its H3K4me3 mark were enriched in response to ethanol.
conclusionsEthanol directly influences HSC transdifferentiation by stimulating global changes in chromatin structure, resulting in the increased expression of ECM proteins. The ability of alcohol to remodel the epigenome during HSC transdifferentiation provides mechanisms for it to act as a co-morbidity factor in liver disease.
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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.