ArticlePLoS genetics2020
Loss of hepatocyte cell division leads to liver inflammation and fibrosis.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Life history enlightened therapies: cell cycle mapping to identify molecular targets to prevent hepatocellular carcinoma.Evolution, medicine, and public health · 2026Article
- Chemical Switching: A Concept Inspired by Strategies from Biocatalysis and Organocatalysis.Chembiochem : a European journal of chemical biology · 2025Review
- Morpho-histological and Transcriptome Analysis Reveal the Unreduced Sperm Formation Mechanism in cdk1-Depletion Zebrafish.Marine biotechnology (New York, N.Y.) · 2024Article
- A network-based transcriptomic landscape of HepG2 cells uncovering causal gene-cytotoxicity interactions underlying drug-induced liver injury.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Targeting ketone body metabolism to treat fatty liver disease.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2024Review
- Hepatocyte integrity depends on c-Jun-controlled proliferation in Schistosoma mansoni infected mice.Scientific reports · 2023Article
- Epithelial mechanics are maintained by inhibiting cell fusion with age in Drosophila.Journal of cell science · 2023Article
- Assessment of Drug-Induced Liver Injury through Cell Morphology and Gene Expression Analysis.Chemical research in toxicology · 2023Article
- Nonalcoholic steatohepatitis-related hepatocellular carcinoma: pathogenesis and treatment.Nature reviews. Gastroenterology & hepatology · 2023Review
- System Biology Investigation Revealed Lipopolysaccharide and Alcohol-Induced Hepatocellular Carcinoma Resembled Hepatitis B Virus Immunobiology and Pathogenesis.International journal of molecular sciences · 2023Article
- Effect of Hepatic Pathology on Liver Regeneration: The Main Metabolic Mechanisms Causing Impaired Hepatic Regeneration.International journal of molecular sciences · 2023Review
- Fat storage-inducing transmembrane proteins: beyond mediating lipid droplet formation.Cellular & molecular biology letters · 2022Review
- Polyploidization of Hepatocytes: Insights into the Pathogenesis of Liver Diseases.Biomolecules & therapeutics · 2022Review
- Article
- Centriole signaling restricts hepatocyte ploidy to maintain liver integrity.Genes & development · 2022Article
- Wnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Alterations in hepatic mitotic and cell cycle transcriptional networks during the metabolic switch in broiler chicks.Frontiers in physiology · 2022Article
- Assessment of Hepatocyte Ploidy by Flow Cytometry.Methods in molecular biology (Clifton, N.J.) · 2022Article
- The role of p53 in liver fibrosis.Frontiers in pharmacology · 2022Review
- Communal living: the role of polyploidy and syncytia in tissue biology.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The liver possesses a remarkable regenerative capacity based partly on the ability of hepatocytes to re-enter the cell cycle and divide to replace damaged cells. This capability is substantially reduced upon chronic damage, but it is not clear if this is a cause or consequence of liver disease. Here, we investigate whether blocking hepatocyte division using two different mouse models affects physiology as well as clinical liver manifestations like fibrosis and inflammation. We find that in P14 Cdk1Liv-/- mice, where the division of hepatocytes is abolished, polyploidy, DNA damage, and increased p53 signaling are prevalent. Cdk1Liv-/- mice display classical markers of liver damage two weeks after birth, including elevated ALT, ALP, and bilirubin levels, despite the lack of exogenous liver injury. Inflammation was further studied using cytokine arrays, unveiling elevated levels of CCL2, TIMP1, CXCL10, and IL1-Rn in Cdk1Liv-/- liver, which resulted in increased numbers of monocytes. Ablation of CDK2-dependent DNA re-replication and polyploidy in Cdk1Liv-/- mice reversed most of these phenotypes. Overall, our data indicate that blocking hepatocyte division induces biological processes driving the onset of the disease phenotype. It suggests that the decrease in hepatocyte division observed in liver disease may not only be a consequence of fibrosis and inflammation, but also a pathological cue.
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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.