ArticlePloS one2017
Systematic integrative analysis of gene expression identifies HNF4A as the central gene in pathogenesis of non-alcoholic steatohepatitis.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals.Communications biology · 2019Pooled it
- Polymorphic variants in Sweet and Umami taste receptor genes and birthweight.Scientific reports · 2021Trial
- Exploring the prediction model and core genes for coronary artery disease in non-obese steatotic liver disease patients.Frontiers in medicine · 2026Article
- ATF3 and HNF4A: an oxidative phosphorylation and cholesterol homeostasis-associated diagnostic and therapeutic repurposing framework target for metabolic dysfunction-associated steatohepatitis patients.Frontiers in medicine · 2026Article
- Gradual DNA methylation changes reveal transcription factors implicated in metabolic dysfunction-associated steatotic liver disease progression and epigenetic age acceleration.Clinical epigenetics · 2025Article
- Sex Hormone-Binding Globulin and Metabolic Syndrome in Children and Adolescents: A Focus on Puberty.Metabolites · 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 IL-34 and Slc7al as potential key regulators in MASLD progression through epigenomic profiling.Epigenomics · 2025Article
- Article
- Machine learning-based integration identifies the ferroptosis hub genes in nonalcoholic steatohepatitis.Lipids in health and disease · 2024Article
- Pharmacologic inhibition of HNF4α prevents parenteral nutrition associated cholestasis in mice.Scientific reports · 2023Article
- HNF4α in Hepatocyte Health and Disease.Seminars in liver disease · 2023Review
- PPARα activation partially drives NAFLD development in liver-specific Hnf4a-null mice.Journal of biochemistry · 2023Article
- HNF4α is possibly the missing link between epithelial-mesenchymal transition and Warburg effect during hepatocarcinogenesis.Cancer science · 2023Article
- Achieving tolerance modifies cancer susceptibility profiles in liver transplant recipients.Cancer medicine · 2023Article
- Comprehensive analysis of ceRNA network composed of circRNA, miRNA, and mRNA in septic acute kidney injury patients based on RNA-seq.Frontiers in genetics · 2023Article
- Expression of p-STAT3 and c-Myc correlates with P2-HNF4α expression in nonalcoholic fatty liver disease (NAFLD).Oncotarget · 2022Article
- 3D-Epigenomic Regulation of Gene Transcription in Hepatocellular Carcinoma.Advanced genetics (Hoboken, N.J.) · 2022Article
- Regulation of Hepatocyte Nuclear Factor 4α Attenuated Lipotoxicity but Increased Bile Acid Toxicity in Non-Alcoholic Fatty Liver Disease.Life (Basel, Switzerland) · 2022Article
- Progressive loss of hepatocyte nuclear factor 4 alpha activity in chronic liver diseases in humans.Hepatology (Baltimore, Md.) · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world, and encompasses a spectrum from simple steatosis to steatohepatitis (NASH). There is currently no approved pharmacologic therapy against NASH, partly due to an incomplete understanding of its molecular basis. The goal of this study was to determine the key differentially expressed genes (DEGs), as well as those genes and pathways central to its pathogenesis. We performed an integrative computational analysis of publicly available gene expression data in NASH from GEO (GSE17470, GSE24807, GSE37031, GSE89632). The DEGs were identified using GEOquery, and only the genes present in at least three of the studies, to a total of 190 DEGs, were considered for further analyses. The pathways, networks, molecular interactions, functional analyses were generated through the use of Ingenuity Pathway Analysis (IPA). For selected networks, we computed the centrality using igraph package in R. Among the statistically significant predicted networks (p-val < 0.05), three were of most biological interest: the first is involved in antimicrobial response, inflammatory response and immunological disease, the second in cancer, organismal injury and development and the third in metabolic diseases. We discovered that HNF4A is the central gene in the network of NASH connected to metabolic diseases and that it regulates HNF1A, an additional transcription regulator also involved in lipid metabolism. Therefore, we show, for the first time to our knowledge, that HNF4A is central to the pathogenesis of NASH. This adds to previous literature demonstrating that HNF4A regulates the transcription of genes involved in the progression of NAFLD, and that HNF4A genetic variants play a potential role in NASH progression.
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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.