ArticleMicrovascular research2015
Junctional complex and focal adhesion rearrangement mediates pulmonary endothelial barrier enhancement by FTY720 S-phosphonate.
Article in Microvascular research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Review
- Genetic and epigenetic regulation of cortactin (CTTN) by inflammatory factors and mechanical stress in human lung endothelial cells.Bioscience reports · 2024Article
- Mechanisms of pulmonary endothelial barrier dysfunction in acute lung injury and acute respiratory distress syndrome.Chinese medical journal pulmonary and critical care medicine · 2024Article
- Lamellipodia dynamics and microrheology in endothelial cell paracellular gap closure.Biophysical journal · 2023Article
- Dialogue between VE-Cadherin and Sphingosine 1 Phosphate Receptor1 (S1PR1) for Protecting Endothelial Functions.International journal of molecular sciences · 2023Review
- Alveolus analysis: a web browser-based tool to analyze lung intravital microscopy.BMC pulmonary medicine · 2022Article
- Tight Junctions, the Epithelial Barrier, and Toll-like Receptor-4 During Lung Injury.Inflammation · 2022Review
- Cortactin in Lung Cell Function and Disease.International journal of molecular sciences · 2022Review
- MRSA-induced endothelial permeability and acute lung injury are attenuated by FTY720 S-phosphonate.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Phosphoproteome profiling provides insight into the mechanisms of ventilator-induced lung injury.Experimental and therapeutic medicine · 2020Article
- Focal adhesion kinase and Src mediate microvascular hyperpermeability caused by fibrinogen- γC- terminal fragments.PloS one · 2020Article
- Article
- Sphingosine 1-Phosphate (S1P)/ S1P Receptor Signaling and Mechanotransduction: Implications for Intrinsic Tissue Repair/Regeneration.International journal of molecular sciences · 2019Review
- Sphingosine-1-Phosphate Reduces Hemorrhagic Shock and Resuscitation-Induced Microvascular Leakage by Protecting Endothelial Mitochondrial Integrity.Shock (Augusta, Ga.) · 2019Article
- Relationship between G proteins coupled receptors and tight junctions.Tissue barriers · 2018Review
- Colquhounia Root Tablet Protects Rat Pulmonary Microvascular Endothelial Cells against TNF-Evidence-based complementary and alternative medicine : eCAM · 2018Article
- Cortical Actin Dynamics in Endothelial Permeability.Current topics in membranes · 2018Article
- Sphingolipids Signaling in Lamellipodia Formation and Enhancement of Endothelial Barrier Function.Current topics in membranes · 2018Article
- Sphingosine-1-Phosphate Treatment Can Ameliorate Microvascular Leakage Caused by Combined Alcohol Intoxication and Hemorrhagic Shock.Scientific reports · 2017Article
- α2-adrenoreceptor modulated FAK pathway induced by dexmedetomidine attenuates pulmonary microvascular hyper-permeability following kidney injury.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
rationaleModulation of pulmonary vascular barrier function is an important clinical goal given the devastating effects of vascular leak in acute lung injury (ALI). We previously demonstrated that FTY720 S-phosphonate (Tys), an analog of sphingosine 1-phosphate (S1P) and FTY720, has more potent pulmonary barrier protective effects than these agents in vitro and in mouse models of ALI. Tys preserves expression of the barrier-promoting S1P1 receptor (S1PR1), whereas S1P and FTY720 induce its ubiquitination and degradation. Here we further characterize the novel barrier promoting effects of Tys in cultured human pulmonary endothelial cells (EC). METHODS/
resultsIn human lung EC, Tys significantly increased peripheral redistribution of adherens junction proteins VE-cadherin and β-catenin and tight junction protein ZO-1. Inhibition of VE-cadherin with blocking antibody significantly attenuated Tys-induced transendothelial resistance (TER) elevation, while ZO-1 siRNA partially inhibited this elevation. Tys significantly increased focal adhesion formation and phosphorylation of focal adhesion kinase (FAK). Pharmacologic inhibition of FAK significantly attenuated Tys-induced TER elevation. Tys significantly increased phosphorylation and peripheral redistribution of the actin-binding protein, cortactin, while cortactin siRNA partially attenuated Tys-induced TER elevation. Although Tys significantly increased phosphorylation of Akt and GSK3β, neither PI3 kinase nor GSK3β inhibition altered Tys-induced TER elevation. Tys significantly increased Rac1 activity, while inhibition of Rac1 activity significantly attenuated Tys-induced VE-cadherin redistribution and TER elevation.
conclusionJunctional complex, focal adhesion rearrangement and Rac1 activation play critical roles in Tys-mediated barrier protection in pulmonary EC. These results provide mechanistic insights into the effects of this potential ALI therapy.
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