ArticleJournal of hepatology2016
Bromodomain and extraterminal (BET) proteins regulate biliary-driven liver regeneration.
Article in Journal of hepatology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
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- BRD4 promotes endodermal cell fate during mammalian lung development.JCI insight · 2026Article
- Massive hepatic necrosis-associated acute liver failure.eGastroenterology · 2026Review
- In toto live imaging of Erk signaling dynamics in developing zebrafish hepatocytes.Developmental biology · 2025Article
- Review
- Negative cell cycle regulation by calcineurin is necessary for proper beta cell regeneration in zebrafish.eLife · 2024Article
- BRD4: an effective target for organ fibrosis.Biomarker research · 2024Review
- The multi-CDK inhibitor dinaciclib reverses bromo- and extra-terminal domain (BET) inhibitor resistance in acute myeloid leukemia via inhibition of Wnt/β-catenin signaling.Experimental hematology & oncology · 2024Article
- Using different zebrafish models to explore liver regeneration.Frontiers in cell and developmental biology · 2024Review
- VEGFA mRNA-LNP promotes biliary epithelial cell-to-hepatocyte conversion in acute and chronic liver diseases and reverses steatosis and fibrosis.Cell stem cell · 2023Article
- PPARα activation promotes liver progenitor cell-mediated liver regeneration by suppressing YAP signaling in zebrafish.Scientific reports · 2023Article
- Update on Hepatobiliary Plasticity.Seminars in liver disease · 2023Article
- DNA methylation in cell plasticity and malignant transformation in liver diseases.Pharmacology & therapeutics · 2023Review
- Role of the Hippo pathway in liver regeneration and repair: recent advances.Inflammation and regeneration · 2022Review
- DNA methylation maintenance at the p53 locus initiates biliary-mediated liver regeneration.NPJ Regenerative medicine · 2022Article
- Farnesoid X Receptor Activation Impairs Liver Progenitor Cell-Mediated Liver Regeneration via the PTEN-PI3K-AKT-mTOR Axis in Zebrafish.Hepatology (Baltimore, Md.) · 2021Article
- Attenuating the Epidermal Growth Factor Receptor-Extracellular Signal-Regulated Kinase-Sex-Determining Region Y-Box 9 Axis Promotes Liver Progenitor Cell-Mediated Liver Regeneration in Zebrafish.Hepatology (Baltimore, Md.) · 2021Article
- Contributions of biliary epithelial cells to hepatocyte homeostasis and regeneration in zebrafish.iScience · 2021Article
- Zebra-Fishing for Regenerative Awakening in Mammals.Biomedicines · 2021Review
- All routes lead to Rome: multifaceted origin of hepatocytes during liver regeneration.Cell regeneration (London, England) · 2021Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsDuring liver regeneration, hepatocytes are derived from pre-existing hepatocytes. However, if hepatocyte proliferation is compromised, biliary epithelial cells (BECs) become the source of new hepatocytes. We recently reported on a zebrafish liver regeneration model in which BECs extensively contribute to hepatocytes. Using this model, we performed a targeted chemical screen to identify important factors that regulate BEC-driven liver regeneration, the mechanisms of which remain largely unknown.
methodsUsing Tg(fabp10a:CFP-NTR) zebrafish, we examined the effects of 44 selected compounds on BEC-driven liver regeneration. Liver size was assessed by fabp10a:DsRed expression; liver marker expression was analyzed by immunostaining, in situ hybridization and quantitative PCR. Proliferation and apoptosis were also examined. Moreover, we used a mouse liver injury model, choline-deficient, ethionine-supplemented (CDE) diet.
resultsWe identified 10 compounds that affected regenerating liver size. Among them, only bromodomain and extraterminal domain (BET) inhibitors, JQ1 and iBET151, blocked both Prox1 and Hnf4a induction in BECs. BET inhibition during hepatocyte ablation blocked BEC dedifferentiation into hepatoblast-like cells (HB-LCs). Intriguingly, after JQ1 washout, liver regeneration resumed, indicating temporal, but not permanent, perturbation of liver regeneration by BET inhibition. BET inhibition after hepatocyte ablation suppressed the proliferation of newly generated hepatocytes and delayed hepatocyte maturation. Importantly, Myca overexpression, in part, rescued the proliferation defect. Furthermore, oval cell numbers in mice fed CDE diet were greatly reduced upon JQ1 administration, supporting the zebrafish findings.
conclusionsBET proteins regulate BEC-driven liver regeneration at multiple steps: BEC dedifferentiation, HB-LC proliferation, the proliferation of newly generated hepatocytes, and hepatocyte maturation.
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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.