ArticleCommunications biology2024
Endothelial ROBO4 suppresses PTGS2/COX-2 expression and inflammatory diseases.
Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Multi-Omics Integration Identifies PTGS2 as a Candidate Diagnostic Biomarker and Precise Therapeutic Target Related to Schisandra chinensis for Osteoarthritis.Chemical biology & drug design · 2026Article
- Antioxidant and Antihypertensive Activities of Ficus exasperata Vahl Leaves: Integrated In Vitro Evaluation and In Silico Multi-Target Mechanistic Insights.Chemistry & biodiversity · 2026Article
- Unraveling Effects and Pharmacological Mechanisms of Phellodendrine on Inflammatory Bowel Disease.Biomolecules · 2026Article
- Assessing the Safety and Efficacy of Agonistic Monoclonal Antibody against Robo4 versus Ranibizumab in Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Phase I, Open-Label, Multicenter Study.Ophthalmology science · 2026Article
- Computational and preliminary screening of anti-caries active compounds of Caesalpinia sappan.Scientific reports · 2026Article
- The Small Molecule Compound Eupalinolide B Ameliorates Depressive Behaviors and Neuropathic Pain in Mice With Spared Nerve Injury: Integrating Network Pharmacology, Molecular Docking, Bioinformatics, Molecular Dynamics Simulation and Experimental Verification.CNS neuroscience & therapeutics · 2026Article
- Natural products in treating sepsis-associated lung and liver injuries by mediating ferroptosis, current progress, and future perspective.Frontiers in pharmacology · 2026Review
- Ursolic acid mitigates hepatic ischemia-reperfusion injury by regulating the ALOX12/12(S)-HETE and PTGES/prostaglandin E2 axis via arachidonic acid metabolism pathway.Frontiers in pharmacology · 2026Article
- Elucidating the Mechanism of Xiaoqinglong Decoction in Chronic Urticaria Treatment: An Integrated Approach of Network Pharmacology, Bioinformatics Analysis, Molecular Docking, and Molecular Dynamics Simulations.Current computer-aided drug design · 2026Article
- The identification of metabolites from gut microbiota in HPV infection via network pharmacology.PloS one · 2026Article
- Identification and Analysis of Biomarkers Associated With Lipid Metabolism and Ferroptosis in Ulcerative Colitis.Journal of immunology research · 2026Article
- TRAF7 in signaling and disease: emerging mechanisms and clinical implications.Molecular medicine (Cambridge, Mass.) · 2025Review
- PTGS2 Silencing Inhibits Ferroptosis in Staphylococcus Aureus-induced Osteomyelitis By Blocking the IL-17A Signaling Pathway.Inflammation · 2025Article
- Review of the Role of TRAF7 in Brain Endothelial Integrity and Cerebrovascular Aging.Life (Basel, Switzerland) · 2025Review
- Machine learning identification of key genes in cardioembolic stroke and atherosclerosis: their association with pan-cancer and immune cells.European journal of medical research · 2025Article
- How endothelial cell metabolism shapes blood-brain barrier integrity in neurodegeneration.Frontiers in molecular neuroscience · 2025Review
- Exploring the Therapeutic Potential of Rutin in Psoriasis: Network Pharmacology and Experimental Validation.Combinatorial chemistry & high throughput screening · 2025Article
- Curdione combined with borneol treats bacterial mixed HPV infection by regulating the crosstalk among immune cells.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Accumulating evidence suggests that endothelial cells can be useful therapeutic targets. One of the potential targets is an endothelial cell-specific protein, Roundabout4 (ROBO4). ROBO4 has been shown to ameliorate multiple diseases in mice, including infectious diseases and sepsis. However, its mechanisms are not fully understood. In this study, using RNA-seq analysis, we found that ROBO4 downregulates prostaglandin-endoperoxide synthase 2 (PTGS2), which encodes cyclooxygenase-2. Mechanistic analysis reveals that ROBO4 interacts with IQ motif-containing GTPase-activating protein 1 (IQGAP1) and TNF receptor-associated factor 7 (TRAF7), a ubiquitin E3 ligase. In this complex, ROBO4 enhances IQGAP1 ubiquitination through TRAF7, inhibits prolonged RAC1 activation, and decreases PTGS2 expression in inflammatory endothelial cells. In addition, Robo4-deficiency in mice exacerbates PTGS2-associated inflammatory diseases, including arthritis, edema, and pain. Thus, we reveal the molecular mechanism by which ROBO4 suppresses the inflammatory response and vascular hyperpermeability, highlighting its potential as a promising therapeutic target for inflammatory diseases.
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