ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2016
Hepatocyte nuclear factor 4α is required for cell differentiation and homeostasis in the adult mouse gastric epithelium.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Cellular plasticity as a therapeutic vulnerability: HNF4α is a key target in lung adenocarcinoma.The Journal of clinical investigation · 2026Article
- HNF4α controls growth, identity, and KRAS inhibitor response in invasive mucinous adenocarcinoma of the lung.The Journal of clinical investigation · 2026Article
- Stomach at the crossroads: nuclear receptor signaling at the interface between what we are and what we eat.Physiological reviews · 2026Review
- The role of HNF4α in adenocarcinoma.Biochemical Society transactions · 2026Review
- Life-long microbiome rejuvenation improves intestinal barrier function and inflammaging in mice.Microbiome · 2025Article
- Expression patterns of HNF4α, TTF-1, and SMARCA4 in lung adenocarcinomas: impacts on clinicopathological and genetic features.Virchows Archiv : an international journal of pathology · 2025Article
- Metabolic regulator ERRγ governs gastric stem cell differentiation into acid-secreting parietal cells.Cell stem cell · 2024Article
- Decoding spatiotemporal transcriptional dynamics and epithelial fibroblast crosstalk during gastroesophageal junction development through single cell analysis.Nature communications · 2024Article
- Gastric intestinal metaplasia: progress and remaining challenges.Journal of gastroenterology · 2024Review
- Phosphomannomutase 2 (PMM2) variants leading to hyperinsulinism-polycystic kidney disease are associated with early-onset inflammatory bowel disease and gastric antral foveolar hyperplasia.Human genetics · 2023Article
- HNF4α isoforms: the fraternal twin master regulators of liver function.Frontiers in endocrinology · 2023Review
- ELAPOR1 is a secretory granule maturation-promoting factor that is lost during paligenosis.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- Article
- Silencing of long non-coding RNA XIST represses gastric cancer progression through blocking NFκB pathway via inhibiting HNF4A-mediated transcription of EPHA1.Cancer gene therapy · 2021Article
- Epithelial expression of Gata4 and Sox2 regulates specification of the squamous-columnar junction via MAPK/ERK signaling in mice.Nature communications · 2021Article
- Hepatocyte nuclear factor 4α and cancer-related cell signaling pathways: a promising insight into cancer treatment.Experimental & molecular medicine · 2021Review
- A Metformin-Responsive Metabolic Pathway Controls Distinct Steps in Gastric Progenitor Fate Decisions and Maturation.Cell stem cell · 2020Article
- Role of hepatocyte nuclear factor 4-alpha in gastrointestinal and liver diseases.World journal of gastroenterology · 2019Review
- Unravel the molecular mechanism of XBP1 in regulating the biology of cancer cells.Journal of Cancer · 2019Review
- Induction of Hepatic Metabolic Functions by a Novel Variant of Hepatocyte Nuclear Factor 4γ.Molecular and cellular biology · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We have previously shown that the sequential transcription factors Xbp1→Mist1 (Bhlha15) govern the ultrastructural maturation of the secretory apparatus in enzyme-secreting zymogenic chief cells (ZCs) in the gastric unit. Here we sought to identify transcriptional regulators upstream of X-box binding protein 1 (XBP1) and MIST1. We used immunohistochemistry to characterize Hnf4α(flox/flox) adult mouse stomachs after tamoxifen-induced deletion of Hnf4α We used qRT-PCR, Western blotting, and chromatin immunoprecipitation to define the molecular interaction between hepatocyte nuclear factor 4 alpha (HNF4α) and Xbp1 in mouse stomach and human gastric cells. We show that HNF4α protein is expressed in pit (foveolar) cells, mucous neck cells, and zymogenic chief cells (ZCs) of the corpus gastric unit. Loss of HNF4α in adult mouse stomach led to reduced ZC size and ER content, phenocopying previously characterized effects of Xbp1 deletion. However, HNF4α(Δ/Δ) stomachs also exhibited additional phenotypes including increased proliferation in the isthmal stem cell zone and altered mucous neck cell migration, indicating a role of HNF4α in progenitor cells as well as in ZCs. HNF4α directly occupies the Xbp1 promoter locus in mouse stomach, and forced HNF4α expression increased abundance of XBP1 mRNA in human gastric cancer cells. Finally, as expected, loss of HNF4α caused decreased Xbp1 and Mist1 expression in mouse stomachs. We show that HNF4α regulates homeostatic proliferation in the gastric epithelium and is both necessary and sufficient for the upstream regulation of the Xbp1→Mist1 axis in maintenance of ZC secretory architecture.
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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.