ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2013
Hepatocyte-specific deletion of hepatocyte nuclear factor-4α in adult mice results in increased hepatocyte proliferation.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 97 citations in OpenAlex.
- Comparison of phenotypic and transcriptomic profiles between HFPO-DA and prototypical PPARα, PPARγ, and cytotoxic agents in wild-type and Ppara-null mouse livers.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- HNF4A mitigates sepsis-associated lung injury by upregulating NCOR2/GR/STAB1 axis and promoting macrophage polarization towards M2 phenotype.Cell death & disease · 2025Article
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Overexpression ofBioMed research international · 2025Article
- Regulation of hepatic xenosensor function by HNF4alpha.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Wnt/β-catenin signaling pathway in liver biology and tumorigenesis.In vitro cellular & developmental biology. Animal · 2024Review
- HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements.Communications biology · 2024Article
- Article
- Ypel5 regulates liver development and function in zebrafish.Journal of molecular cell biology · 2023Article
- HNF4α in Hepatocyte Health and Disease.Seminars in liver disease · 2023Review
- Interleukin-1ß Attenuates Expression of Augmenter of Liver Regeneration (ALR) by Regulating HNF4α Independent of c-Jun.International journal of molecular sciences · 2023Article
- HNF4α isoforms regulate the circadian balance between carbohydrate and lipid metabolism in the liver.Frontiers in endocrinology · 2023Article
- Hepatic circadian and differentiation factors control liver susceptibility for fatty liver disease and tumorigenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Adipose tissue-specific ablation of Ces1d causes metabolic dysregulation in mice.Life science alliance · 2022Article
- Progressive loss of hepatocyte nuclear factor 4 alpha activity in chronic liver diseases in humans.Hepatology (Baltimore, Md.) · 2022Article
- Article
- Male-Specific Activation of Lysine Demethylases 5B and 5C Mediates Alcohol-Induced Liver Injury and Hepatocyte Dedifferentiation.Hepatology communications · 2022Article
- PXR activation impairs hepatic glucose metabolism partlyActa pharmaceutica Sinica. B · 2022Article
- Regulation of Liver Regeneration by Hepatocyte O-GlcNAcylation in Mice.Cellular and molecular gastroenterology and hepatology · 2022Article
- Role and Regulation of Wnt/β-Catenin in Hepatic Perivenous Zonation and Physiological Homeostasis.The American journal of pathology · 2022Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Hepatocyte nuclear factor-4α (HNF4α) is known as the master regulator of hepatocyte differentiation. Recent studies indicate that HNF4α may inhibit hepatocyte proliferation via mechanisms that have yet to be identified. Using a HNF4α knockdown mouse model based on delivery of inducible Cre recombinase via an adeno-associated virus 8 viral vector, we investigated the role of HNF4α in the regulation of hepatocyte proliferation. Hepatocyte-specific deletion of HNF4α resulted in increased hepatocyte proliferation. Global gene expression analysis showed that a majority of the downregulated genes were previously known HNF4α target genes involved in hepatic differentiation. Interestingly, ≥500 upregulated genes were associated with cell proliferation and cancer. Furthermore, we identified potential negative target genes of HNF4α, many of which are involved in the stimulation of proliferation. Using chromatin immunoprecipitation analysis, we confirmed binding of HNF4α at three of these genes. Furthermore, overexpression of HNF4α in mouse hepatocellular carcinoma cells resulted in a decrease in promitogenic gene expression and cell cycle arrest. Taken together, these data indicate that, apart from its role in hepatocyte differentiation, HNF4α actively inhibits hepatocyte proliferation by repression of specific promitogenic genes.
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Registered trials
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.