ArticleHepatology (Baltimore, Md.)2008
Hepatocyte nuclear factor 4alpha is implicated in endoplasmic reticulum stress-induced acute phase response by regulating expression of cyclic adenosine monophosphate responsive element binding protein H.
Article in Hepatology (Baltimore, Md.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
60 citing papers in PubMed, 104 citations in OpenAlex.
- Dietary protein restriction reduces circulating VLDL triglyceride levels via CREBH-APOA5-dependent and -independent mechanisms.JCI insight · 2018Trial
- Biomarkers for early identification of metabolic dysfunction-associated steatotic liver disease (MASLD): a narrative review.Archives of medical science : AMS · 2026Article
- Homeostasis control in health and disease by the unfolded protein response.Nature reviews. Molecular cell biology · 2025Review
- Disruption of the creb3l1 gene causes defects in caudal fin regeneration and patterning in zebrafish Danio rerio.Developmental dynamics : an official publication of the American Association of Anatomists · 2024Article
- Downregulation of HNF4A enables transcriptomic reprogramming during the hepatic acute-phase response.Communications biology · 2024Article
- The Regulatory Network of CREB3L1 and Its Roles in Physiological and Pathological Conditions.International journal of medical sciences · 2024Review
- CREB-H is a stress-regulator of hepcidin gene expression during early postnatal development.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Role of hepcidin upregulation and proteolytic cleavage of ferroportin 1 in hepatitis C virus-induced iron accumulation.PLoS pathogens · 2023Article
- Akkermansia muciniphila and its membrane protein ameliorates intestinal inflammatory stress and promotes epithelial wound healing via CREBH and miR-143/145.Journal of biomedical science · 2023Article
- A hepatokine derived from the ER protein CREBH promotes triglyceride metabolism by stimulating lipoprotein lipase activity.Science signaling · 2023Article
- Regulation of Hepatocyte Nuclear Factor 4α Attenuated Lipotoxicity but Increased Bile Acid Toxicity in Non-Alcoholic Fatty Liver Disease.Life (Basel, Switzerland) · 2022Article
- Single-cell chromatin profiling of the primitive gut tube reveals regulatory dynamics underlying lineage fate decisions.Nature communications · 2022Article
- Gadd45 in the Liver: Signal Transduction and Transcriptional Mechanisms.Advances in experimental medicine and biology · 2022Article
- Stress-induced Regulators of Intestinal Fat Absorption.Cellular and molecular gastroenterology and hepatology · 2022Article
- Adipose expression of CREB3L3 modulates body weight during obesity.Scientific reports · 2021Article
- CREBH Systemically Regulates Lipid Metabolism by Modulating and Integrating Cellular Functions.Nutrients · 2021Review
- The transcription factors CREBH, PPARa, and FOXO1 as critical hepatic mediators of diet-induced metabolic dysregulation.The Journal of nutritional biochemistry · 2021Review
- MBTPS2, a membrane bound protease, underlying several distinct skin and bone disorders.Journal of translational medicine · 2021Review
- Review
- Synergistic regulation of hepatic Fsp27b expression by HNF4α and CREBH.Biochemical and biophysical research communications · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledLoss of the nuclear hormone receptor hepatocyte nuclear factor 4alpha (HNF4alpha) in hepatocytes results in a complex pleiotropic phenotype that includes a block in hepatocyte differentiation and a severe disruption to liver function. Recent analyses have shown that hepatic gene expression is severely affected by the absence of HNF4alpha, with expression of 567 genes reduced by > or =2.5-fold (P < or = 0.05) in Hnf4alpha(-/-) fetal livers. Although many of these genes are direct targets, HNF4alpha has also been shown to regulate expression of other liver transcription factors, and this raises the possibility that the dependence on HNF4alpha for normal expression of some genes may be indirect. We postulated that the identification of transcription factors whose expression is regulated by HNF4alpha might reveal roles for HNF4alpha in controlling hepatic functions that were not previously appreciated. Here we identify cyclic adenosine monophosphate responsive element binding protein H (CrebH) as a transcription factor whose messenger RNA can be identified in both the embryonic mouse liver and adult mouse liver and whose expression is dependent on HNF4alpha. Analyses of genomic DNA revealed an HNF4alpha binding site upstream of the CrebH coding sequence that was occupied by HNF4alpha in fetal livers and facilitated transcriptional activation of a reporter gene in transient transfection analyses. Although CrebH is highly expressed during hepatogenesis, CrebH(-/-) mice were viable and healthy and displayed no overt defects in liver formation. However, upon treatment with tunicamycin, which induces an endoplasmic reticulum (ER)-stress response, CrebH(-/-) mice displayed reduced expression of acute phase response proteins.
conclusionThese data implicate HNF4alpha in having a role in controlling the acute phase response of the liver induced by ER stress by regulating expression of CrebH.
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Registered trials
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