ArticleJournal of lipid research2017
FoxO3 increases miR-34a to cause palmitate-induced cholangiocyte lipoapoptosis.
Article in Journal of lipid research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- Altered cholangiocyte subsets with neural pathway enrichment in metabolic dysfunction-associated steatotic liver disease.Internal and emergency medicine · 2026Article
- MicroRNA-34a Promotes Hepatic Lipid Accumulation Through RXRα Suppression and Is Reversed by 9-International journal of molecular sciences · 2026Article
- FOXO: a key target in regulating aging and age-related diseases.Biogerontology · 2026Review
- MicroRNA: A Novel Class of Potential Biomarkers and Therapeutic Target for Non-Alcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis.MicroRNA (Shariqah, United Arab Emirates) · 2025Review
- Honey vesicle-like nanoparticles protect aged liver from non-alcoholic steatohepatitis.Acta pharmaceutica Sinica. B · 2024Article
- Palmitate induces integrated stress response and lipoapoptosis in trophoblasts.Cell death & disease · 2024Article
- MicroRNAs Differentially Expressed in Actinic Keratosis and Healthy Skin Scrapings.Biomedicines · 2023Article
- The zhuyu pill relieves rat cholestasis by regulating the mRNA expression of lipid and bile metabolism associated genes.Frontiers in pharmacology · 2023Article
- Cellular heterogeneity and plasticity during NAFLD progression.Frontiers in molecular biosciences · 2023Review
- Role of FOXO3a Transcription Factor in the Regulation of Liver Oxidative Injury.Antioxidants (Basel, Switzerland) · 2022Review
- Mitochondrial Dysfunction and Acute Fatty Liver of Pregnancy.International journal of molecular sciences · 2022Review
- HES5-mediated repression of LIGHT transcription may contribute to apoptosis in hepatocytes.Cell death discovery · 2021Article
- Impact of Dietary Fat on the Progression of Liver Fibrosis: Lessons from Animal and Cell Studies.International journal of molecular sciences · 2021Review
- Acetylcholine reduces palmitate-induced cardiomyocyte apoptosis by promoting lipid droplet lipolysis and perilipin 5-mediated lipid droplet-mitochondria interaction.Cell cycle (Georgetown, Tex.) · 2021Article
- Modeling alcohol-associated liver disease in a human Liver-Chip.Cell reports · 2021Article
- Biliary Epithelial Senescence in Liver Disease: There Will Be SASP.Frontiers in molecular biosciences · 2021Review
- MicroRNAs in the Pathogenesis of Nonalcoholic Fatty Liver Disease.International journal of biological sciences · 2021Review
- Article
- Targeting the microRNA-34a as a Novel Therapeutic Strategy for Cardiovascular Diseases.Frontiers in cardiovascular medicine · 2021Review
- Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Nonalcoholic steatohepatitis (NASH) patients have elevated plasma saturated free fatty acid levels. These toxic fatty acids can induce liver cell death and our recent results demonstrated that the biliary epithelium may be susceptible to lipotoxicity. Here, we explored the molecular mechanisms of cholangiocyte lipoapoptosis in cell culture and in an animal model of NASH. Treatment of cholangiocytes with palmitate (PA) showed increased caspase 3/7 activity and increased levels of cleaved poly (ADP-ribose) polymerase and cleaved caspase 3, demonstrating cholangiocyte lipoapoptosis. Interestingly, treatment with PA significantly increased the levels of microRNA miR-34a, a pro-apoptotic microRNA known to be elevated in NASH. PA induction of miR-34a was abolished in cholangiocytes transduced with forkhead family of transcription factor class O (FoxO)3 shRNA, demonstrating that FoxO3 activation is upstream of miR-34a and suggesting that FoxO3 is a novel transcriptional regulator of miR-34a. Further, anti-miR-34a protected cholangiocytes from PA-induced lipoapoptosis. Direct and indirect targets of miR-34a, such as SIRT1, receptor tyrosine kinase (MET), Kruppel-like factor 4, fibroblast growth factor receptor (FGFR)1, and FGFR4, were all decreased in PA-treated cholangiocytes. SIRT1 and MET were partially rescued by a miR-34a antagonist. Cholangiocyte apoptosis and miR-34a were dramatically increased in the liver of mice with early histologic features of NASH. Our study provides evidence for the pro-apoptotic role of miR-34a in PA-induced cholangiocyte lipoapoptosis in culture and in the liver.
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Registered trials
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