ArticleCell death & disease2018
Ethanol sensitizes hepatocytes for TGF-β-triggered apoptosis.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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Who cites it
15 citing papers in PubMed, 31 citations in OpenAlex.
- Alcohol-driven phenotypic transition in MASLD and risk of liver-related events.JHEP reports : innovation in hepatology · 2026Article
- Transforming Growth Factor-β Signaling in Alcohol-Associated Liver Disease: A Multicellular Perspective.The American journal of pathology · 2026Review
- Article
- Altered polyadenylation site usage in SERPINA1 3'UTR in response to cellular stress affects A1AT protein expression.Scientific reports · 2025Article
- Subchondral injection of human umbilical cord mesenchymal stem cells ameliorates knee osteoarthritis by inhibiting osteoblast apoptosis and TGF-beta activity.Stem cell research & therapy · 2025Article
- Dual signaling pathways of TGF-β superfamily cytokines in hepatocytes: balancing liver homeostasis and disease progression.Frontiers in pharmacology · 2025Review
- Review
- Effect of Europinidin against Alcohol-Induced Liver Damage in Rats by Inhibiting the TNF-α/TGF-β/IFN-γ/NF-kB/Caspase-3 Signaling Pathway.ACS omega · 2023Article
- Withaferin A alleviates ethanol-induced liver injury by inhibiting hepatic lipogenesis.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2022Article
- Downmodulation of Regulatory T Cells Producing TGF-β Participates in Pathogenesis of Leprosy Reactions.Frontiers in medicine · 2022Article
- Chronic Alcohol Exposure Among People Living with HIV Is Associated with Innate Immune Activation and Alterations in Monocyte Phenotype and Plasma Cytokine Profile.Frontiers in immunology · 2022Article
- Gut microbiota and their metabolites in the progression of non-alcoholic fatty liver disease.Hepatoma research · 2021Article
- Pathophysiology of hepatic NaExperimental and therapeutic medicine · 2020Review
- Berberine inhibits epithelial-mesenchymal transition and promotes apoptosis of tumour-associated fibroblast-induced colonic epithelial cells through regulation of TGF-β signalling.Journal of cell communication and signaling · 2020Article
- Mangosteen Hinders Gamma Radiation-Mediated Oxidative Stress and Liver Injury by Down-Regulating TNF-α/NF-κB and Pro-Fibrotic Factor TGF-β1 Inducing Inflammatory Signaling.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
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Authors and funding
16 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alcohol abuse is a global health problem causing a substantial fraction of chronic liver diseases. Abundant TGF-β-a potent pro-fibrogenic cytokine-leads to disease progression. Our aim was to elucidate the crosstalk of TGF-β and alcohol on hepatocytes. Primary murine hepatocytes were challenged with ethanol and TGF-β and cell fate was determined. Fluidigm RNA analyses revealed transcriptional effects that regulate survival and apoptosis. Mechanistic insights were derived from enzyme/pathway inhibition experiments and modulation of oxidative stress levels. To substantiate findings, animal model specimens and human liver tissue cultures were investigated.
resultsOn its own, ethanol had no effect on hepatocyte apoptosis, whereas TGF-β increased cell death. Combined treatment led to massive hepatocyte apoptosis, which could also be recapitulated in human HCC liver tissue treated ex vivo. Alcohol boosted the TGF-β pro-apoptotic gene signature. The underlying mechanism of pathway crosstalk involves SMAD and non-SMAD/AKT signaling. Blunting CYP2E1 and ADH activities did not prevent this effect, implying that it was not a consequence of alcohol metabolism. In line with this, the ethanol metabolite acetaldehyde did not mimic the effect and glutathione supplementation did not prevent the super-induction of cell death. In contrast, blocking GSK-3β activity, a downstream mediator of AKT signaling, rescued the strong apoptotic response triggered by ethanol and TGF-β. This study provides novel information on the crosstalk between ethanol and TGF-β. We give evidence that ethanol directly leads to a boost of TGF-β's pro-apoptotic function in hepatocytes, which may have implications for patients with chronic alcoholic 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.