ArticleThe Journal of biological chemistry2009
Tiam1 and Rac1 are required for platelet-activating factor-induced endothelial junctional disassembly and increase in vascular permeability.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 98 citations in OpenAlex.
- Thromborepair: the tissue repair partner to thromboinflammation.Blood vessels, thrombosis & hemostasis · 2026Review
- Piperine alleviates retinal ischemic injury by mediating the APE1 signaling.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Anthrax ET activates Rac1 and RTK signaling to induce F-actin reorganization and endothelial permeability.iScience · 2025Article
- Novel Metabolites Genetically Linked to Salt Sensitivity of Blood Pressure: Evidence from mGWAS in Chinese Population.International journal of molecular sciences · 2025Article
- Mortality Risk Analysis of Combination Antiplatelet Therapy in Patients with Ischemic Stroke and Acute Kidney Injury: A Retrospective Cohort Analysis of the MIMIC-IV Database.Diseases (Basel, Switzerland) · 2025Article
- Targeting vascular endothelial growth receptor-2 (VEGFR-2): structural biology, functional insights, and therapeutic resistance.Archives of pharmacal research · 2025Review
- Molecular Mechanisms Regulating Vascular Endothelial Permeability.International journal of molecular sciences · 2024Review
- Platelet-Activating Factor Receptor (PAFR) Regulates Retinal Progenitor/Stem Cells Profile in Ciliary Epithelium Cells.International journal of molecular sciences · 2024Article
- PRGF Membrane with Tailored Optical Properties Preserves the Cytoprotective Effect of Plasma Rich in Growth Factors: In Vitro Model of Retinal Pigment Epithelial Cells.International journal of molecular sciences · 2023Article
- Feedback between mechanosensitive signaling and active forces governs endothelial junction integrity.Nature communications · 2022Article
- Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility.Nature genetics · 2022Article
- Review
- Molecular Dambusters: What Is Behind Hyperpermeability in Bradykinin-Mediated Angioedema?Clinical reviews in allergy & immunology · 2021Review
- In Vitro Investigation of Vascular Permeability in Endothelial Cells from Human Artery, Vein and Lung Microvessels at Steady-State and Anaphylactic Conditions.Biomedicines · 2021Article
- Subcellular hot spots of GPCR signaling promote vascular inflammation.Current opinion in endocrine and metabolic research · 2021Review
- The contribution of platelets to intravascular arrest, extravasation, and outgrowth of disseminated tumor cells.Clinical & experimental metastasis · 2020Review
- Effect of Platelet-Activating Factor on Barrier Function of ARPE-19 Cells.Drug design, development and therapy · 2020Article
- A nonapoptotic endothelial barrier-protective role for caspase-3.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Small GTPases and Their Role in Vascular Disease.International journal of molecular sciences · 2019Review
- Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
It is known that platelet-activating factor (PAF) induces severe endothelial barrier leakiness, but the signaling mechanisms remain unclear. Here, using a wide range of biochemical and morphological approaches applied in both mouse models and cultured endothelial cells, we addressed the mechanisms of PAF-induced disruption of interendothelial junctions (IEJs) and of increased endothelial permeability. The formation of interendothelial gaps filled with filopodia and lamellipodia is the cellular event responsible for the disruption of endothelial barrier. We observed that PAF ligation of its receptor induced the activation of the Rho GTPase Rac1. Following PAF exposure, both Rac1 and its guanine nucleotide exchange factor Tiam1 were found associated with a membrane fraction from which they co-immunoprecipitated with PAF receptor. In the same time frame with Tiam1-Rac1 translocation, the junctional proteins ZO-1 and VE-cadherin were relocated from the IEJs, and formation of numerous interendothelial gaps was recorded. Notably, the response was independent of myosin light chain phosphorylation and thus distinct from other mediators, such as histamine and thrombin. The changes in actin status are driven by the PAF-induced localized actin polymerization as a consequence of Rac1 translocation and activation. Tiam1 was required for the activation of Rac1, actin polymerization, relocation of junctional associated proteins, and disruption of IEJs. Thus, PAF-induced IEJ disruption and increased endothelial permeability requires the activation of a Tiam1-Rac1 signaling module, suggesting a novel therapeutic target against increased vascular permeability associated with inflammatory diseases.
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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.