ArticleThe Journal of biological chemistry2010
Thrombospondin-1 inhibits VEGF receptor-2 signaling by disrupting its association with CD47.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers.
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Who cites it
152 citing papers in PubMed, 223 citations in OpenAlex.
- Fibulin-1 is required for microvascular integrity in the developing brain and retina.Developmental biology · 2026Article
- Research advances on CD47 in digestive system cancers: from molecular mechanisms to clinical translation.Molecular medicine (Cambridge, Mass.) · 2026Review
- Matricellular Proteins in Bladder Cancer: Context-Dependent Roles in Tumor Promotion and Suppression.International journal of molecular sciences · 2026Review
- Targeting the CD47-SIRPα phagocytic checkpoint in cancer: Biology, translational opportunities, and next-generation therapeutic strategies.Smart molecules : open access · 2026Review
- Donation After Circulatory Death Islets are Comparable to Standard-of-Care Donation After Brain Death Islets: Analysis of 801 Consecutive Human Islet Isolations.Transplantation direct · 2026Article
- Thrombospondin 1 aggravates cardiac remodeling in heart failure with preserved ejection fraction by inhibiting mitophagy.iScience · 2026Article
- Rab37-mediated OPN secretion enriches SPP1Oncogenesis · 2026Article
- Uncovering the Role of Thrombospodin-1 and Occludin as Potential Prognostic and Diagnostic Biomarkers in Traumatic Brain Injury.International journal of molecular sciences · 2026Article
- The CD47 signaling axis regulates the formation and vulnerability of atherosclerotic plaques: mechanism analysis and targeting strategies.Frontiers in immunology · 2026Review
- The role of thrombospondin-1 in dermatological conditions.Frontiers in medicine · 2026Review
- Role of Extracellular Vesicles in Skin Barrier Repair: Applications in Atopic Dermatitis and Chronic Wounds.International journal of nanomedicine · 2026Review
- Review
- Interleukin 10 enhances endothelial progenitor cell-mediated angiogenesis in extrahepatic portal venous obstruction.Stem cell research & therapy · 2025Article
- The Glycosaminoglycan-Dependent Interactome of Neurexin-1 in Human Fetal Glial Cells.Proteoglycan research · 2025Article
- The mechanobiology of extracellular matrix: a focus on thrombospondins.Cell communication and signaling : CCS · 2025Review
- CD47-mediated tumor microenvironment remodeling: a central mechanism in immune evasion.Acta biochimica et biophysica Sinica · 2025Review
- CD47-mediated regulation of glucose and lipid metabolism: implications for the pathogenesis of MASLD.Frontiers in endocrinology · 2025Review
- Deciphering the role of signal regulatory protein α in immunotherapy for solid tumors.Frontiers in immunology · 2025Review
- CD47 signaling induces hepatic cell death and microglia activation during hepatic encephalopathy.Metabolic brain disease · 2024Article
- Thrombospondin 1 Mediates Autophagy Upon Inhibition of the Rho-Associated Protein Kinase Inhibitor.Cells · 2024Article
92 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Thrombospondin-1 (TSP1) can inhibit angiogenic responses directly by interacting with VEGF and indirectly by engaging several endothelial cell TSP1 receptors. We now describe a more potent mechanism by which TSP1 inhibits VEGF receptor-2 (VEGFR2) activation through engaging its receptor CD47. CD47 ligation is known to inhibit downstream signaling targets of VEGFR2, including endothelial nitric-oxide synthase and soluble guanylate cyclase, but direct effects on VEGFR2 have not been examined. Based on FRET and co-immunoprecipitation, CD47 constitutively associated with VEGFR2. Ligation of CD47 by TSP1 abolished resonance energy transfer with VEGFR2 and inhibited phosphorylation of VEGFR2 and its downstream target Akt without inhibiting VEGF binding to VEGFR2. The inhibitory activity of TSP1 in large vessel and microvascular endothelial cells was replicated by a recombinant domain of the protein containing its CD47-binding site and by a CD47-binding peptide derived from this domain but not by the CD36-binding domain of TSP1. Inhibition of VEGFR2 phosphorylation was lost when CD47 expression was suppressed in human endothelial cells and in murine CD47-null cells. These results reveal that anti-angiogenic signaling through CD47 is highly redundant and extends beyond inhibition of nitric oxide signaling to global inhibition of VEGFR2 signaling.
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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.