ArticleJournal of biomedical science2018
Cells responsible for liver mass regeneration in rats with 2-acetylaminofluorene/partial hepatectomy injury.
Article in Journal of biomedical science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Retrorsine impairs liver regeneration by inducing progenitor cell-senescenceAnnals of medicine · 2026Article
- A Protocol for the Isolation of Oval Cells without Preconditioning.International journal of molecular sciences · 2024Article
- Granulocyte colony-stimulating factor attenuates liver damage by M2 macrophage polarization and hepatocyte proliferation in alcoholic hepatitis in mice.Hepatology communications · 2022Article
- p53 positively regulates the proliferation of hepatic progenitor cells promoted by laminin-521.Signal transduction and targeted therapy · 2022Article
- Enrichment of progenitor cells by 2-acetylaminofluorene accelerates liver carcinogenesis induced by diethylnitrosamine in vivo.Molecular carcinogenesis · 2021Article
- [Research progress on the relationship between non-coding RNA and liver regeneration].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2021Review
- Establishment of an Immunocompetent Metastasis Rat Model with Hepatocyte Cancer Stem Cells.Cancers · 2020Article
- Founder cells for hepatocytes during liver regeneration: from identification to application.Cellular and molecular life sciences : CMLS · 2020Review
- Hepatic progenitor cell activation is induced by the depletion of the gut microbiome in mice.MicrobiologyOpen · 2019Article
- RETRACTED: Regulation of Long Non-Coding RNA-Dreh Involved in Proliferation and Migration of Hepatic Progenitor Cells during Liver Regeneration in Rats.International journal of molecular sciences · 2019Article
- Autophagy promotes hepatic differentiation of hepatic progenitor cells by regulating the Wnt/β-catenin signaling pathway.Journal of molecular histology · 2019Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundWhether hepatic progenitor cells (HPCs)/oval cells regenerate liver mass upon chronic liver injury is controversial in mice and has not been conclusively proven in humans and rats. In this study, we examined which cell type-hepatocytes or oval cells-mediates liver regeneration in the classic rat 2-acetylaminofluorene (AAF)/partial hepatectomy (PH) injury where AAF reversibly blocks hepatocyte proliferation, thereby inducing oval cell expansion after the regenerative stimulus of PH.
methodsWe employed lineage tracing of dipeptidyl peptidase IV (DPPIV, a hepatocyte canalicular enzyme)-positive hepatocytes by subjecting rats with DPPIV-chimeric livers to AAF/PH, AAF/PH/AAF (continuous AAF after AAF/PH to nonselectively inhibit regenerating hepatocytes), or AAF/PH/retrorsine injury (2-dose retrorsine after AAF/PH to specifically and irreversibly block existing hepatocytes); through these methods, we determined hepatocyte contribution to liver regeneration. To determine the oval cell contribution to hepatocyte regeneration, we performed DPPIV(+) oval cell transplantation combined with AAF/PH injury or AAF/PH/retrorsine injury in DPPIV-deficient rats to track the fate of DPPIV(+) oval cells.
resultsDPPIV-chimeric livers demonstrated typical oval cell activation upon AAF/PH injury. After cessation of AAF, DPPIV(+) hepatocytes underwent extensive proliferation to regenerate the liver mass, whereas oval cells underwent hepatocyte differentiation. Upon AAF/PH/AAF injury where hepatocyte proliferation was inhibited by continuous AAF treatment following AAF/PH, oval cells extensively expanded in an undifferentiated state but did not produce hepatocytes. By substituting retrorsine for AAF administration following AAF/PH (AAF/PH/retrorsine), oval cells regenerated large-scale hepatocytes.
conclusionsHepatocyte self-replication provides the majority of hepatocyte regeneration, with supplementary contribution from oval cells in rats under AAF/PH injury. Oval cells expand and maintain in an undifferentiated state upon continuously nonselective liver injury, whereas they can significantly regenerate hepatocytes in a noncompetitive environment.
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