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| Autores principales: | , , , , , , , |
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| Formato: | Artículo científico |
| Lenguaje: | en |
| Publicado: |
Development (Cambridge, England)
2025
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| Materias: | |
| Acceso en línea: | https://pubmed.ncbi.nlm.nih.gov/39976298/ |
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- Activation of prep expression by Tet2 promotes the proliferation of bipotential progenitor cells during liver regeneration. Jia, Kun Cheng, Bo Huang, Lirong Xu, Jiaxin Liu, Fasheng Liao, Xinjun Liao, Kai Lu, Huiqiang Animals Cell Proliferation Liver Regeneration Zebrafish DNA-Binding Proteins Stem Cells Serine Endopeptidases DNA Methylation Zebrafish Proteins Signal Transduction Dioxygenases Proto-Oncogene Proteins Proto-Oncogene Proteins c-akt TOR Serine-Threonine Kinases Phosphatidylinositol 3-Kinases Liver DNA Demethylation Epithelial Cells Promoter Regions, Genetic Biliary epithelial cell (BEC)-derived liver regeneration in zebrafish exhibits similarities to liver regeneration in chronic liver injury. However, the underlying mechanisms remain poorly understood. Here, we identified a serine peptidase called prolyl endopeptidase (Prep) as an indispensable factor during the BEC-derived liver regeneration process. prep was significantly upregulated and enriched in bipotential progenitor cells (BP-PCs). Through gain- and loss-of-function assays, prep was found to potently accelerate liver regeneration and drastically increase the proliferation of BP-PCs. Mechanistically, prep expression was directly regulated by ten-eleven translocation 2 (Tet2)-mediated DNA demethylation. More strikingly, Tet2 regulated prep expression by directly interacting and reducing the methylation of CpG sites in the prep promoter. Subsequently, Prep activated the PI3K-AKT-mTOR signaling pathway to regulate liver regeneration. Therefore, our study revealed the role and mechanism of Tet2-mediated DNA demethylation-associated upregulation of prep in the proliferation of BP-PCs during liver regeneration. These results identify promising targets for stimulating regeneration following chronic liver injury.