ArticleCellular signalling2018
EphA2 stimulates VCAM-1 expression through calcium-dependent NFAT1 activity.
Article in Cellular signalling, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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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
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Gene expression regulation by CaCellular & molecular biology letters · 2026Pooled it
- Fibronectin-dependent integrin signaling drives EphA2 expression in vascular smooth muscle cells.American journal of physiology. Cell physiology · 2025Article
- Recent advances of the Ephrin and Eph family in cardiovascular development and pathologies.iScience · 2024Review
- Article
- Nuclear factor of activated T-cells (NFAT) regulation of IL-1β-induced retinal vascular inflammation.Biochimica et biophysica acta. Molecular basis of disease · 2021Article
- Cooperation between CYB5R3 and NOX4 via coenzyme Q mitigates endothelial inflammation.Redox biology · 2021Article
- EphA2 signaling within integrin adhesions regulates fibrillar adhesion elongation and fibronectin deposition.Matrix biology : journal of the International Society for Matrix Biology · 2021Article
- Ginsenoside Rg5 inhibits cancer cell migration by inhibiting the nuclear factor-κB and erythropoietin-producing hepatocellular receptor A2 signaling pathways.Oncology letters · 2021Article
- Neuronal guidance proteins in cardiovascular inflammation.Basic research in cardiology · 2021Review
- Ephs and Ephrins in Adult Endothelial Biology.International journal of molecular sciences · 2020Review
- Approaches to Manipulate Ephrin-A:EphA Forward Signaling Pathway.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Endothelial Cell Calcium Signaling during Barrier Function and Inflammation.The American journal of pathology · 2020Review
- Host deficiency in ephrin-A1 inhibits breast cancer metastasis.F1000Research · 2020Article
- Emerging Roles for Eph Receptors and Ephrin Ligands in Immunity.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Endothelial cell activation by proinflammatory stimuli drives leukocyte recruitment through enhanced expression of counter-receptors such as vascular cell adhesion molecule-1 (VCAM-1). We previously demonstrated that activation of the receptor tyrosine kinase EphA2 with its ligand ephrin-A1 induces VCAM-1 expression. Here, we sought to characterize the proinflammatory signaling pathways involved. Analysis of over-represented transcription factors in ephrin-A1-induced genes identified multiple potential transcriptional regulators, including the Rel family members nuclear factor-κB (NF-κB/p65) and nuclear factor of activated T-cells (NFAT). While ephrin-A1 failed to induce endothelial NF-κB activation, NF-κB inhibitors prevented ephrin-A1-induced VCAM-1 expression, suggesting basal NF-κB activity is required. In contrast, ephrin-A1 induced a robust EphA2-dependent increase in NFAT activation, and mutation of the NF-κB/NFAT-binding sites in the VCAM-1 promoter blunted ephrin-A1-induced promoter activity. NFAT activation classically occurs through calcium-dependent calcineurin activation, and inhibiting NFAT signaling with calcineurin inhibitors (cyclosporine A, FK506) or direct NFAT inhibitors (A-285222) was sufficient to block ephrin-A1-induced VCAM-1 expression. Consistent with robust NFAT activation, ephrin-A1-induced an EphA2-dependent calcium influx in endothelial cells that was required for ephrin-A1-induced NFAT activation and VCAM-1 expression. This work provides the first data showing EphA2-dependent calcium influx and NFAT activation and identifies NFAT as a novel EphA2-dependent proinflammatory pathway in endothelial activation.
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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.