ArticleProceedings of the National Academy of Sciences of the United States of America2005
S1P3 receptor-induced reorganization of epithelial tight junctions compromises lung barrier integrity and is potentiated by TNF.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 63 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
63 citing papers in PubMed, 128 citations in OpenAlex.
- Pharmacokinetics, Pharmacodynamics, Tolerability, and Food Effect of Cenerimod, a Selective S1P₁ Receptor Modulator in Healthy Subjects.International journal of molecular sciences · 2017Trial
- Pharmacokinetics and pharmacodynamics of ponesimod, a selective S1P1 receptor modulator, in the first-in-human study.British journal of clinical pharmacology · 2013Trial
- Short-Term Acid Sphingomyelinase Deficiency Exerts Proinflammatory and Antiapoptotic Effects during LPS-induced Lung Injury in Mice.American journal of respiratory cell and molecular biology · 2025Article
- Tetraspanin-enriched membrane domains regulate vascular leakage by altering membrane cholesterol accessibility to balance antagonistic GTPases.Nature cardiovascular research · 2025Article
- Unique pharmacological properties of etrasimod among S1P receptor modulators.FEBS open bio · 2025Article
- Modulation of IL-4/IL-13 cytokine signaling in the context of allergic disease.The Journal of allergy and clinical immunology · 2022Review
- The Sphingosine Kinase 2 Inhibitor Opaganib Protects Against Acute Kidney Injury in Mice.International journal of nephrology and renovascular disease · 2022Article
- Serum sphingosine-1-phosphate levels in bladder pain syndrome/interstitial cystitis patients: could it help in diagnosis?World journal of urology · 2020Article
- Overexpression of Sphingosine Kinase-1 and Sphingosine-1-Phosphate Receptor-3 in SevereBioMed research international · 2020Article
- Sphingosine-1-phosphate signaling and the gut-liver axis in liver diseases.Liver research (Beijing, China) · 2019Article
- Article
- Sphingosine Kinases/Sphingosine 1-Phosphate Signaling in Hepatic Lipid Metabolism.Current pharmacology reports · 2017Article
- Cytokine-Ion Channel Interactions in Pulmonary Inflammation.Frontiers in immunology · 2017Review
- Activated tumor cell integrin αvβ3 cooperates with platelets to promote extravasation and metastasis from the blood stream.Thrombosis research · 2016Article
- Pulmonary endothelial cell barrier enhancement by novel FTY720 analogs: methoxy-FTY720, fluoro-FTY720, and β-glucuronide-FTY720.Chemistry and physics of lipids · 2015Article
- Sphingosine-1-phosphate receptor 1 agonism attenuates lung ischemia-reperfusion injury.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Bile acids and sphingosine-1-phosphate receptor 2 in hepatic lipid metabolism.Acta pharmaceutica Sinica. B · 2015Review
- Role of Sphingolipids in the Pathobiology of Lung Inflammation.Mediators of inflammation · 2015Review
- Article
- Suppression of inflammation and acute lung injury by Miz1 via repression of C/EBP-δ.Nature immunology · 2013Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
- Retraction · 2009-07-09Results Not Reproducible · · BA 6/7/17
- Retracted
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Pulmonary pathologies including adult respiratory distress syndrome are characterized by disruption of pulmonary integrity and edema compromising respiratory function. Sphingosine 1-phosphate (S1P) is a lipid mediator synthesized and/or stored in mast cells, platelets, and epithelial cells, with production up-regulated by the proinflammatory cytokines IL-1 and TNF. S1P administration via the airways but not via the vasculature induces lung leakage. Using receptor-null mice, we show that S1P, acting on S1P3 receptor expressed on both type I and type II alveolar epithelial cells but not vascular endothelium, induces pulmonary edema by acute tight junction opening. WT but not S1P3-null mice showed disruption of pulmonary epithelial tight junctions and the appearance of paracellular gaps between epithelial cells by electron microscopy within 1 h of airways exposure to S1P. We further show by fluorescence microscopy that S1P induced rapid loss of ZO-1 reactivity, an essential component of the cytoplasmic plaque associated with tight junctions, as well as of the tetraspannin Claudin-18, an integral membrane organizer of tight junctions. S1P shows synergistic activity with the proinflammatory cytokine TNF, showing both pulmonary edema and mortality at subthreshold S1P doses. Specifically, preexposure of mice to subthreshold doses of TNF, which alone induced no lung edema, exacerbated S1P-induced edema and impaired survival. S1P, acting through S1P3, regulates epithelial integrity and acts additively with TNF in compromising respiratory barrier function. Because S1P3-null mice are resistant to S1P-induced pulmonary leakage, either alone or in the presence of TNF, S1P3 antagonism may be useful in protecting epithelial integrity in pulmonary disease.
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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.