ArticleThe Journal of clinical investigation2002
Ecto-5'-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia.
Article in The Journal of clinical investigation, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 467 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
467 citing papers in PubMed, 677 citations in OpenAlex.
- Boosting CAR T cell efficacy in cancer with metabolic insights from design to diet.Nature reviews. Cancer · 2026Review
- CD73 inhibition overcomes adaptive immune resistance to PARP inhibition in models of prostate cancer.The Journal of clinical investigation · 2026Article
- The role of hypoxia-inducible factors in myocardial ischaemia-reperfusion injury and cardioprotection.Nature reviews. Cardiology · 2026Review
- Spatially organized regulated cell death-immune coupling in solid tumors: integrating spatial omics with actionable regulated cell death biology.Molecular cancer · 2026Review
- Immunometabolic Stress and Immune Suppression in Clear-Cell Renal Cell Carcinoma: Perspectives in Therapeutic Strategy.International journal of molecular sciences · 2026Review
- GBP5 Aggravates Acute Lung Injury Via NLRP3 Inflammasome Activation While Inducing a HIF-1α-CD73-adenosine Feedback Loop.Inflammation · 2026Article
- Targeting conserved domains of hypoxia-inducible factors for cancer therapy.The Journal of experimental medicine · 2026Article
- Intestinal epithelial Smad7 drives purine metabolic dysregulation and ileal inflammation.Journal of biomedical science · 2026Article
- Spatiotemporal dynamics of ecto-5'-nucleotidase (CD73) in mouse retina under physiological conditions.Development (Cambridge, England) · 2026Article
- Potent Competitive Inhibitors of Ecto-5'-nucleotidase (CD73) based on 6‑(Het)aryl-7-deazapurine Ribonucleoside 5'‑ACS pharmacology & translational science · 2026Article
- The macrophage opera: from metabolic prolog to oncogenic crescendo in metabolic dysfunction-associated steatotic liver disease.Frontiers in medicine · 2026Review
- Targeting ecto-5'-nucleotidase (CD73) and cAMP alleviates carotid body hyperactivity and reduces blood pressure in chronically hypoxic rats.The Journal of physiology · 2026Article
- Impact of Neutrophils on the Tissue Microenvironment During Intestinal Inflammation.Journal of inflammation research · 2026Review
- Nanomaterials Reshaping Tumor Metabolism: A New Frontier to Overcome T Cell Exhaustion.International journal of nanomedicine · 2026Review
- The CD39-CD73-adenosine axis: a pivotal regulator of retinal homeostasis and diseases.Frontiers in cell and developmental biology · 2026Review
- CD73 is associated with glycolysis related metabolic programs and CD8Frontiers in immunology · 2026Article
- Dynamic regulation of hypoxia-associated regulatory CD39Frontiers in immunology · 2026Article
- Hypoxia-Induced Gut-Brain Axis Remodeling and Insomnia: Mechanisms and Microbiota Adaptive Regulation from a Translational Perspective.Journal of inflammation research · 2026Review
- Synergistic Inhibition of Angiogenesis and Tumor Progression by CD73 Inhibitor and Menstrual Blood Stem Cell-Derived Exosomes via miR-422a Upregulation in HER2-Positive Breast Cancer.Cancer management and research · 2026Article
- Restoring adenosine balance in axial spondyloarthritis: a stage-specific framework for immune and structural modulation.Frontiers in immunology · 2026Review
407 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Under conditions of limited oxygen availability (hypoxia), multiple cell types release adenine nucleotides in the form of ATP, ADP, and AMP. Extracellular AMP is metabolized to adenosine by surface-expressed ecto-5'-nucleotidase (CD73) and subsequently activates surface adenosine receptors regulating endothelial and epithelial barrier function. Therefore, we hypothesized that hypoxia transcriptionally regulates CD73 expression. Microarray RNA analysis revealed an increase in CD73 and ecto-apyrase CD39 in hypoxic epithelial cells. Metabolic studies of CD39/CD73 function in intact epithelia revealed that hypoxia enhances CD39/CD73 function as much as 6 +/- 0.5-fold over normoxia. Examination of the CD73 gene promoter identified at least one binding site for hypoxia-inducible factor-1 (HIF-1) and inhibition of HIF-1alpha expression by antisense oligonucleotides resulted in significant inhibition of hypoxia-inducible CD73 expression. Studies using luciferase reporter constructs revealed a significant increase in activity in cells subjected to hypoxia, which was lost in truncated constructs lacking the HIF-1 site. Mutagenesis of the HIF-1alpha binding site resulted in a nearly complete loss of hypoxia-inducibility. In vivo studies in a murine hypoxia model revealed that hypoxia-induced CD73 may serve to protect the epithelial barrier, since the CD73 inhibitor alpha,beta-methylene ADP promotes increased intestinal permeability. These results identify an HIF-1-dependent regulatory pathway for CD73 and indicate the likelihood that CD39/CD73 protects the epithelial barrier during hypoxia.
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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.