ArticleScientific reports2022
Hypoxia-induced HIF1α activation regulates small extracellular vesicle release in human embryonic kidney cells.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 38 citations in OpenAlex.
- Endothelial-Derived Extracellular Vesicles During Exercise in COPD Patients.The clinical respiratory journal · 2025Trial
- Hypoxia-programmed apoptotic-mimetic M2 macrophage-derived small extracellular vesicles for hydrogel-mediated immunoregenerative bone repair.Materials today. Bio · 2026Article
- Trophoblast derived extracellular vesicles trigger secondary vesicle release from endometrial epithelial cells.Cell communication and signaling : CCS · 2026Article
- Evaluation of Serum HIF-1α as a Hypoxia-Related Biomarker in Patients with Malignant Salivary Gland Neoplasms.Biomedicines · 2026Article
- Brain targeting and trafficking of extracellular vesicles in central nervous system diseases: a therapeutic roadmap.Nanomedicine (London, England) · 2026Review
- A review of recent advances in exosome-mediated drug delivery for regenerative therapy and immunomodulation.Biomedical engineering online · 2026Review
- Extracellular Vesicles in Liver Disease: Redefining Diagnostic and Therapeutic Strategies.International journal of stem cells · 2026Review
- Review
- From immune desert to hot tumor: the tripartite synergy of tumor microenvironment-exosomes-immunogenic cell death in pioneering solutions.Frontiers in immunology · 2026Review
- Exosomal biomarkers and therapeutics in lung cancer: a narrative review on their role in early detection and targeted treatment.Translational lung cancer research · 2025Review
- Emerging technologies towards extracellular vesicles large-scale production.Bioactive materials · 2025Review
- High-Yield Bioproduction of Extracellular Vesicles from Stem Cell Spheroids via Millifluidic Vortex Transport.Advanced materials (Deerfield Beach, Fla.) · 2025Article
- Effects of small extracellular vesicles derived from normoxia- and hypoxia-treated prostate cancer cells on the submandibular salivary gland epitheliumTissue barriers · 2025Article
- Molecular insights into immune evasion in head and neck squamous cell carcinomas: Toward a promising treatment strategy.Oncology research · 2025Review
- Advancements in extracellular vesicles biomanufacturing: a comprehensive overview of large-scale production and clinical research.Frontiers in bioengineering and biotechnology · 2025Review
- Cancer cell-derived extracellular vesicles: a potential target for overcoming tumor immunotherapy resistance and immune evasion strategies.Frontiers in immunology · 2025Review
- Hypoxia Pathways in Parkinson's Disease: From Pathogenesis to Therapeutic Targets.International journal of molecular sciences · 2024Review
- Lipid droplets and small extracellular vesicles: More than two independent entities.Journal of extracellular biology · 2024Article
- Extracellular Vesicles from Adipose Tissue-Derived Stromal Cells Stimulate Angiogenesis in a Scaffold-Dependent Fashion.Tissue engineering and regenerative medicine · 2024Article
- FunctionalScience advances · 2024Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Extracellular vesicles (EVs) are membrane enclosures released by eukaryotic cells that carry bioactive molecules and serve to modulate biological responses in recipient cells. Both increased EV release and altered EV composition are associated with the development and progression of many pathologies including cancer. Hypoxia, a feature of rapidly growing solid tumours, increases the release of EVs. However, the molecular mechanisms remain unknown. The hypoxia inducible factors (HIFs) are transcription factors that act as major regulators of the cellular adaptations to hypoxia. Here, we investigated the requirement of HIF pathway activation for EV release in Human Embryonic Kidney Cells (HEK293). Time course experiments showed that EV release increased concomitantly with sustained HIF1α and HIF2α activation following the onset of hypoxia. shRNA mediated knock-down of HIF1α but not HIF2α abrogated the effect of hypoxia on EV release, suggesting HIF1α is involved in this process. However, stabilization of HIF proteins in normoxic conditions through: (i) heterologous expression of oxygen insensitive HIF1α or HIF2α mutants in normoxic cells or (ii) chemical inhibition of the prolyl hydroxylase 2 (PHD2) repressor protein, did not increase EV release, suggesting HIF activation alone is not sufficient for this process. Our findings suggest HIF1α plays an important role in the regulation of EV release during hypoxia in HEK293 cells, however other hypoxia triggered mechanisms likely contribute as stabilization of HIF1α alone in normoxia is not sufficient for EV release.
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Registered trials
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