ArticleThe Journal of biological chemistry2012
Suppression of hepatocyte proliferation by hepatocyte nuclear factor 4α in adult mice.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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Who cites it
117 citing papers in PubMed, 209 citations in OpenAlex.
- Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma.Hepatology (Baltimore, Md.) · 2014Trial
- Dynamics and master transcription factors dependence of intestinal super-enhancers during differentiation and oncogenesis.Nucleic acids research · 2026Article
- The role of HNF4α in adenocarcinoma.Biochemical Society transactions · 2026Review
- Article
- Bridging pancreatic and hepatic development: overlapping genes and their role in diabetes.Cellular & molecular biology letters · 2025Review
- Hepatocyte Nuclear Factor 4 Alpha: A Key Regulator of Liver Disease Pathology and Haemostatic Disorders.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Identification of hepatocyte-primed cholangiocytes in the homeostatic liver by in vivo lentiviral gene transfer to mice and non-human primates.Cell reports · 2025Article
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Hypoxia-Inducible Factor-2α Promotes Liver Fibrosis by Inducing Hepatocellular Death.International journal of molecular sciences · 2024Article
- Hepatocyte nuclear factor 4α is a critical factor for the production of complement components in the liver.In vitro cellular & developmental biology. Animal · 2024Article
- Regulation of hepatic xenosensor function by HNF4alpha.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Liver-specific glucocorticoid action in alcoholic liver disease: Study of glucocorticoid receptor knockout and knockin mice.Liver research (Beijing, China) · 2024Article
- HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements.Communications biology · 2024Article
- Spatial and single-cell profiling of the metabolome, transcriptome and epigenome of the aging mouse liver.Nature aging · 2023Article
- Ypel5 regulates liver development and function in zebrafish.Journal of molecular cell biology · 2023Article
- The lncRNA HOTAIR: a pleiotropic regulator of epithelial cell plasticity.Journal of experimental & clinical cancer research : CR · 2023Review
- Transcription factor HNF4α2 promotes osteogenesis and prevents bone abnormalities in mice with renal osteodystrophy.The Journal of clinical investigation · 2023Article
- Hepatocyte Nuclear Factor 4α (HNF4α) Plays a Controlling Role in Expression of the Retinoic Acid Receptor β (International journal of molecular sciences · 2023Article
- HNF4α in Hepatocyte Health and Disease.Seminars in liver disease · 2023Review
- Normalization of hepatic ChREBP activity does not protect against liver disease progression in a mouse model for Glycogen Storage Disease type Ia.Cancer & metabolism · 2023Article
57 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatocyte nuclear factor 4α (HNF4α) regulates genes involved in lipid and bile acid synthesis, gluconeogenesis, amino acid metabolism, and blood coagulation. In addition to its metabolic role, HNF4α is critical for hepatocyte differentiation, and loss of HNF4α is associated with hepatocellular carcinoma. The hepatocyte-specific Hnf4a knock-out mouse develops severe hepatomegaly and steatosis resulting in premature death, thereby limiting studies of the role of this transcription factor in the adult animal. In addition, gene compensation may complicate analysis of the phenotype of these mice. To overcome these issues, an acute Hnf4a knock-out mouse model was generated through use of the tamoxifen-inducible ErT2cre coupled to the serum albumin gene promoter. Microarray expression analysis revealed up-regulation of genes associated with proliferation and cell cycle control only in the acute liver-specific Hnf4α-null mouse. BrdU and ki67 staining confirmed extensive hepatocyte proliferation in this model. Proliferation was associated with induction of the hepatomitogen Bmp7 as well as reduced basal apoptotic activity. The p53/p63 apoptosis effector gene Perp was further identified as a direct HNF4α target gene. These data suggest that HNF4α maintains hepatocyte differentiation in the adult healthy liver, and its loss may directly contribute to hepatocellular carcinoma development, thus indicating this factor as a possible liver tumor suppressor gene.
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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.