ArticleProceedings of the National Academy of Sciences of the United States of America2017
Glucocorticoids promote Von Hippel Lindau degradation and Hif-1α stabilization.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Research progress in the pathogenesis of hormone-induced femoral head necrosis based on microvessels: a systematic review.Journal of orthopaedic surgery and research · 2024Pooled it
- Cancer stem cell plasticity in shaping drug resistance landscapes in prostate cancer.Journal of advanced research · 2026Review
- Evolutionary Integration and Glucocorticoid Regulation of the Respiratory System: Structure, Function, and Homeostatic Adaptation.Medical sciences (Basel, Switzerland) · 2026Review
- Macrophage adaptation to hypoxia in the tuberculous granuloma potentiates mycobacterium-induced mitochondrial damage and granuloma necrosis.bioRxiv : the preprint server for biology · 2026Article
- Systematic and comprehensive insights into HIF-1 stabilization under normoxic conditions: implications for cellular adaptation and therapeutic strategies in cancer.Cellular & molecular biology letters · 2025Review
- Comparative Analysis of the Effects of Maternal Hypoxia and Placental Ischemia on HIF1-Dependent Metabolism and the Glucocorticoid System in the Embryonic and Newborn Rat Brain.International journal of molecular sciences · 2024Article
- Zebrafish polg2 knock-out recapitulates human POLG-disorders; implications for drug treatment.Cell death & disease · 2024Article
- Isolated ACTH deficiency: an uncommon cause of hyperferritinaemia.BMJ case reports · 2023Article
- STAT3 and HIF1α cooperatively mediate the transcriptional and physiological responses to hypoxia.Cell death discovery · 2023Article
- Modeling Human Muscular Dystrophies in Zebrafish: Mutant Lines, Transgenic Fluorescent Biosensors, and Phenotyping Assays.International journal of molecular sciences · 2023Review
- Hypoxia and HIFs in Ewing sarcoma: new perspectives on a multi-facetted relationship.Molecular cancer · 2023Review
- Enhancement of immune surveillance in breast cancer by targeting hypoxic tumor endothelium: Can it be an immunological switch point?Frontiers in oncology · 2023Review
- The impact of hepatocyte-specific deletion of hypoxia-inducible factors on the development of polymicrobial sepsis with focus on GR and PPARα function.Frontiers in immunology · 2023Article
- Article
- Inflammation in Pulmonary Hypertension and Edema Induced by Hypobaric Hypoxia Exposure.International journal of molecular sciences · 2022Review
- Glucocorticoids coordinate macrophage metabolism through the regulation of the tricarboxylic acid cycle.Molecular metabolism · 2022Article
- Zebrafish Mutant Lines Reveal the Interplay betweenInternational journal of molecular sciences · 2022Article
- Reprogramming of glucocorticoid receptor function by hypoxia.EMBO reports · 2022Article
- Hyperactivation of Wnt/β-catenin and Jak/Stat3 pathways in human and zebrafish foetal growth restriction models: Implications for pharmacological rescue.Frontiers in cell and developmental biology · 2022Article
- Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
Glucocorticoid (GC) and hypoxic transcriptional responses play a central role in tissue homeostasis and regulate the cellular response to stress and inflammation, highlighting the potential for cross-talk between these two signaling pathways. We present results from an unbiased in vivo chemical screen in zebrafish that identifies GCs as activators of hypoxia-inducible factors (HIFs) in the liver. GCs activated consensus hypoxia response element (HRE) reporters in a glucocorticoid receptor (GR)-dependent manner. Importantly, GCs activated HIF transcriptional responses in a zebrafish mutant line harboring a point mutation in the GR DNA-binding domain, suggesting a nontranscriptional route for GR to activate HIF signaling. We noted that GCs increase the transcription of several key regulators of glucose metabolism that contain HREs, suggesting a role for GC/HIF cross-talk in regulating glucose homeostasis. Importantly, we show that GCs stabilize HIF protein in intact human liver tissue and isolated hepatocytes. We find that GCs limit the expression of Von Hippel Lindau protein (pVHL), a negative regulator of HIF, and that treatment with the c-src inhibitor PP2 rescued this effect, suggesting a role for GCs in promoting c-src-mediated proteosomal degradation of pVHL. Our data support a model for GCs to stabilize HIF through activation of c-src and subsequent destabilization of pVHL.
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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.