ArticleHepatology communications2022
Male-Specific Activation of Lysine Demethylases 5B and 5C Mediates Alcohol-Induced Liver Injury and Hepatocyte Dedifferentiation.
Article in Hepatology communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Alcohol-induced KDM5B activation in hepatocytes drives pathogenic cell-cell communication, leading to loss of liver function.Hepatology communications · 2025Article
- Sex Differences in Risk of Adverse Liver Events in Patients With Cirrhosis.JAMA network open · 2025Article
- 20(S)-Ginsenoside Rg3 Partially Induces Maturation of HepG2 Cells via the AMPK/HNF4A Pathway.Iranian journal of public health · 2025Article
- Whole exome sequencing analysis identifies genes for alcohol consumption.Nature communications · 2024Article
- Protective role of 17β-estradiol in alcohol-associated liver fibrosis is mediated by suppression of integrin signaling.Hepatology communications · 2024Article
- Alcohol-Associated Liver Disease Outcomes: Critical Mechanisms of Liver Injury Progression.Biomolecules · 2024Review
- Review
- KDM5 Family Demethylase Inhibitor KDOAM-25 Reduces Entry of SARS-CoV-2 Pseudotyped Viral Particles into Cells.Bulletin of experimental biology and medicine · 2023Article
- Histone Demethylation Profiles in Nonalcoholic Fatty Liver Disease and Prognostic Values in Hepatocellular Carcinoma: A Bioinformatic Analysis.Current issues in molecular biology · 2023Article
- Single-Cell RNA Transcriptome Profiling of Liver Cells of Short-Term Alcoholic Liver Injury in Mice.International journal of molecular sciences · 2023Article
- A Pathogenic Role of Non-Parenchymal Liver Cells in Alcohol-Associated Liver Disease of Infectious and Non-Infectious Origin.Biology · 2023Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Alcohol-associated liver disease (ALD) is a major cause of alcohol-related mortality. Sex differences in sensitivity to ALD are well described, but these are often disregarded in studies of ALD development. We aimed to define sex-specific pathways in liver exposed to alcohol. Mice were fed the Lieber-DeCarli alcohol liquid diet or a combination of a high-fat diet with alcohol in water. Single-cell RNA sequencing (scRNA-Seq) was performed on liver cells from male and female mice. Mice were treated with adeno-associated virus (AAV)-short hairpin (sh)Control or AAV-sh lysine demethylase 5b (shKdm5b) and/or AAV-shKdm5c vectors. Changes after Kdm5b/5c knockdown were assessed by RNA-Seq and histone H3 lysine K4 (H3K4)me3 chromatin immunoprecipitation-Seq analysis. Using scRNA-Seq analysis, we found several sex-specific pathways induced by alcohol, including pathways related to lipid metabolism and hepatocyte differentiation. Bioinformatic analysis suggested that two epigenetic regulators, H3K4-specific lysine demethylases KDM5B and KDM5C, contribute to sex differences in alcohol effects. We found that in alcohol-fed male mice, KDM5B and KDM5C are involved in hepatocyte nuclear factor 4 alpha (Hnf4a) down-regulation, hepatocyte dedifferentiation, and an increase in fatty acid synthesis. This effect is mediated by alcohol-induced KDM5B and KDM5C recruitment to Hnf4a and other gene promoters in male but not in female mice. Kdm5b and Kdm5c knockdown or KDM5-inhibitor treatment prevented alcohol-induced lipid accumulation and restored levels of Hnf4a and other hepatocyte differentiation genes in male mice. In addition, Kdm5b knockdown prevented hepatocellular carcinoma development in male mice by up-regulating Hnf4a and decreasing tumor cell proliferation. Conclusion: Alcohol specifically activates KDM5 demethylases in male mice to promote alcohol-induced hepatocyte dedifferentiation and tumor development.
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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.