ArticleCirculation research2009
Akt-mediated transactivation of the S1P1 receptor in caveolin-enriched microdomains regulates endothelial barrier enhancement by oxidized phospholipids.
Article in Circulation research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 111 citations in OpenAlex.
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- Sphingosine-1-phosphate alleviates colitis by regulating macrophage polarization and PI3k-Akt signaling.Frontiers in immunology · 2025Article
- Umbelliferone as an effective component of Rhodiola for protecting the cerebral microvascular endothelial barrier in cSVD.Frontiers in pharmacology · 2025Article
- Edema and lymphatic clearance: molecular mechanisms and ongoing challenges.Clinical science (London, England : 1979) · 2023Review
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- Barrier maintenance by S1P during inflammation and sepsis.Tissue barriers · 2021Review
- Hydrogen Sulfide Actions in the Vasculature.Comprehensive Physiology · 2021Article
- Programming to S1PR1Circulation research · 2021Article
- Oxidized Phospholipids in Control of Endothelial Barrier Function: Mechanisms and Implication in Lung Injury.Frontiers in endocrinology · 2021Review
- Dooming Phagocyte Responses: Inflammatory Effects of Endogenous Oxidized Phospholipids.Frontiers in endocrinology · 2021Review
- Post-translational modifications of S1PR1 and endothelial barrier regulation.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Review
- Extracellular adenosine enhances pulmonary artery vasa vasorum endothelial cell barrier function via Gi/ELMO1/Rac1/PKA-dependent signaling mechanisms.American journal of physiology. Cell physiology · 2020Article
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- The unconventional role of Akt1 in the advanced cancers and in diabetes-promoted carcinogenesis.Pharmacological research · 2019Review
- Mechanosensitive Rap1 activation promotes barrier function of lung vascular endothelium under cyclic stretch.Molecular biology of the cell · 2019Article
- Endothelial Akt1 loss promotes prostate cancer metastasis via β-catenin-regulated tight-junction protein turnover.British journal of cancer · 2018Article
- Lipid mediators in the regulation of endothelial barriers.Tissue barriers · 2018Review
- Sphingolipids Signaling in Lamellipodia Formation and Enhancement of Endothelial Barrier Function.Current topics in membranes · 2018Article
- Sphingosine 1-phosphate (S1P) signalling: Role in bone biology and potential therapeutic target for bone repair.Pharmacological research · 2017Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Endothelial cell (EC) barrier dysfunction results in increased vascular permeability, leading to increased mass transport across the vessel wall and leukocyte extravasation, the key mechanisms in pathogenesis of tissue inflammation and edema. We have previously demonstrated that OxPAPC (oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine) significantly enhances vascular endothelial barrier properties in vitro and in vivo and attenuates endothelial hyperpermeability induced by inflammatory and edemagenic agents via Rac and Cdc42 GTPase dependent mechanisms. These findings suggested potential important therapeutic value of barrier-protective oxidized phospholipids. In this study, we examined involvement of signaling complexes associated with caveolin-enriched microdomains (CEMs) in barrier-protective responses of human pulmonary ECs to OxPAPC. Immunoblotting from OxPAPC-treated ECs revealed OxPAPC-mediated rapid recruitment (5 minutes) to CEMs of the sphingosine 1-phosphate receptor (S1P(1)), the serine/threonine kinase Akt, and the Rac1 guanine nucleotide exchange factor Tiam1 and phosphorylation of caveolin-1, indicative of signaling activation in CEMs. Abolishing CEM formation (methyl-beta-cyclodextrin) blocked OxPAPC-mediated Rac1 activation, cytoskeletal reorganization, and EC barrier enhancement. Silencing (small interfering RNA) Akt expression blocked OxPAPC-mediated S1P(1) activation (threonine phosphorylation), whereas silencing S1P(1) receptor expression blocked OxPAPC-mediated Tiam1 recruitment to CEMs, Rac1 activation, and EC barrier enhancement. To confirm our in vitro results in an in vivo murine model of acute lung injury with pulmonary vascular hyperpermeability, we observed that selective lung silencing of caveolin-1 or S1P(1) receptor expression blocked OxPAPC-mediated protection from ventilator-induced lung injury. Taken together, these results suggest Akt-dependent transactivation of S1P(1) within CEMs is important for OxPAPC-mediated cortical actin rearrangement and EC barrier protection.
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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.