ArticleHepatology (Baltimore, Md.)2011
Hypoxia-inducible transcription factor 2α promotes steatohepatitis through augmenting lipid accumulation, inflammation, and fibrosis.
Article in Hepatology (Baltimore, Md.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 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
113 citing papers in PubMed, 175 citations in OpenAlex.
- Biomarkers of NAFLD progression: a lipidomics approach to an epidemic.Journal of lipid research · 2015Trial
- Divergent Hypoxia-Inducible Factor 2‑Alpha Signaling in Alcoholic Liver Disease and Metabolic Dysfunction-Associated Steatotic Liver Disease.ACS pharmacology & translational science · 2026Review
- Hepatic HIF2α Modulates Extra-Hepatic Disease-Associated Phenotypes During Metabolic Dysfunction-Associated Steatotic Liver Disease.Comprehensive physiology · 2026Article
- Complex interactions between miR-107 and PTEN gene expression, more specifically in viral and NASH cirrhosis.Biochemistry and biophysics reports · 2026Article
- Understanding the role of hypoxia inducible factors in liver fibrosis and future therapeutic applications.iLIVER · 2026Review
- HIF-2α induction in de novo lipogenesis in metabolic dysfunction-associated steatohepatitis is dependent on IL-21 signaling.The Journal of biological chemistry · 2026Article
- Hypoxia-inducible factors in the immunometabolism of metabolic dysfunction-associated steatotic liver disease (MASLD): molecular mechanisms and therapeutic implications.Frontiers in physiology · 2026Article
- Hepatocyte HIF2α Downregulates the Urea Cycle Through Suppression of HNF4α.Gastro hep advances · 2026Article
- The Beauty Sleep to Keep a Healthy Liver.International journal of molecular sciences · 2025Review
- Sleep disorders in hepatocellular carcinoma.World journal of gastrointestinal oncology · 2025Review
- Hypoxia-inducible factor 2 triggers the production of highly infectious native-like hepatitis C virus particles.Cellular and molecular life sciences : CMLS · 2025Article
- Orchestration of Gut-Liver-Associated Transcription Factors in MAFLD: From Cross-Organ Interactions to Therapeutic Innovation.Biomedicines · 2025Review
- Leptin and Insulin in COPD: Unveiling the Metabolic-Inflammatory Axis-A Narrative Review.Journal of clinical medicine · 2025Review
- HIF-3α/PPAR-γ Regulates Hypoxia Tolerance by Altering Glycolysis and Lipid Synthesis in Blunt Snout Bream (International journal of molecular sciences · 2025Article
- A Comprehensive Review of Metabolic Dysfunction-Associated Steatotic Liver Disease: Its Mechanistic Development Focusing on Methylglyoxal and Counterbalancing Treatment Strategies.International journal of molecular sciences · 2025Review
- Hypoxia-Inducible Factor-2α Promotes Liver Fibrosis by Inducing Hepatocellular Death.International journal of molecular sciences · 2024Article
- HIF-2α drives hepatic Kupffer cell death and proinflammatory recruited macrophage activation in nonalcoholic steatohepatitis.Science translational medicine · 2024Article
- Review
- Sphingosine d18:1 promotes nonalcoholic steatohepatitis by inhibiting macrophage HIF-2α.Nature communications · 2024Article
- Steatotic Donor Transplant Livers: Preservation Strategies to Mitigate against Ischaemia-Reperfusion Injury.International journal of molecular sciences · 2024Review
53 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
unlabelledOxygen dynamics in the liver is a central signaling mediator controlling hepatic homeostasis, and dysregulation of cellular oxygen is associated with liver injury. Moreover, the transcription factor relaying changes in cellular oxygen levels, hypoxia-inducible factor (HIF), is critical in liver metabolism, and sustained increase in HIF signaling can lead to spontaneous steatosis, inflammation, and liver tumorigenesis. However, the direct responses and genetic networks regulated by HIFs in the liver are unclear. To help define the HIF signal-transduction pathway, an animal model of HIF overexpression was generated and characterized. In this model, overexpression was achieved by Von Hippel-Lindau (Vhl) disruption in a liver-specific temporal fashion. Acute disruption of Vhl induced hepatic lipid accumulation in an HIF-2α-dependent manner. In addition, HIF-2α activation rapidly increased liver inflammation and fibrosis, demonstrating that steatosis and inflammation are primary responses of the liver to hypoxia. To identify downstream effectors, a global microarray expression analysis was performed using livers lacking Vhl for 24 hours and 2 weeks, revealing a time-dependent effect of HIF on gene expression. Increase in genes involved in fatty acid synthesis were followed by an increase in fatty acid uptake-associated genes, and an inhibition of fatty acid β-oxidation. A rapid increase in proinflammatory cytokines and fibrogenic gene expression was also observed. In vivo chromatin immunoprecipitation assays revealed novel direct targets of HIF signaling that may contribute to hypoxia-mediated steatosis and inflammation.
conclusionThese data suggest that HIF-2α is a critical mediator in the progression from clinically manageable steatosis to more severe steatohepatitis and liver cancer, and may be a potential therapeutic target.
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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.