{"doi":"10.1371/journal.pone.0091346","title":"Sphingosine-1-Phosphate Receptor 3 Mediates Sphingosine-1-Phosphate Induced Release of Weibel-Palade Bodies from Endothelial Cells","abstract":null,"journal":"PLoS ONE","year":2014,"id":602922,"datarank":0.4887144807032224,"base_score":3.258096538021482,"endowment":3.258096538021482,"self_citation_contribution":0.4887144807032224,"citation_network_contribution":0.0,"self_endowment_contribution":0.4887144807032224,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1546511,"name":"Léon J. A. Spijkers","orcid":null,"position":1,"is_corresponding":false},{"id":1546512,"name":"Dorothee van Breevoort","orcid":null,"position":2,"is_corresponding":false},{"id":1546513,"name":"Mar Fernandez-Borja","orcid":null,"position":3,"is_corresponding":false},{"id":1260002,"name":"Ruben Bierings","orcid":"0000-0002-1205-9689","position":4,"is_corresponding":false},{"id":597385,"name":"Jaap D. van Buul","orcid":"0000-0003-0054-7949","position":5,"is_corresponding":false},{"id":1546514,"name":"Astrid E. Alewijnse","orcid":null,"position":6,"is_corresponding":false},{"id":1546516,"name":"Stephan L. M. Peters","orcid":null,"position":7,"is_corresponding":false},{"id":342829,"name":"Jan Voorberg","orcid":"0000-0003-4585-2621","position":8,"is_corresponding":false},{"id":1546510,"name":"Kathinka W. E. M. van Hooren","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Sphingosine-1-Phosphate Receptor 3 Mediates Sphingosine-1-Phosphate Induced Release of Weibel-Palade Bodies from Endothelial Cells","abstract":"Sphingosine-1-phosphate (S1P) is an agonist for five distinct G-protein coupled receptors, that is released by platelets, mast cells, erythrocytes and endothelial cells. S1P promotes endothelial cell barrier function and induces release of endothelial cell-specific storage-organelles designated Weibel-Palade bodies (WPBs). S1P-mediated enhancement of endothelial cell barrier function is dependent on S1P receptor 1 (S1PR1) mediated signaling events that result in the activation of the small GTPase Rac1. Recently, we have reported that Rac1 regulates epinephrine-induced WPB exocytosis following its activation by phosphatidylinositol-3,4,5-triphosphate-dependent Rac exchange factor 1 (PREX1). S1P has also been described to induce WPB exocytosis. Here, we confirm that S1P induces release of WPBs using von Willebrand factor (VWF) as a marker. Using siRNA mediated knockdown of gene expression we show that S1PR1 is not involved in S1P-mediated release of WPBs. In contrast depletion of the S1PR3 greatly reduced S1P-induced release of VWF. S1P-mediated enhancement of endothelial barrier function was not affected by S1PR3-depletion whereas it was greatly impaired in cells lacking S1PR1. The Rho kinase inhibitor Y27632 completely abrogated S1P-mediated release of VWF. Also, the calcium chelator BAPTA-AM significantly reduced S1P-induced release of VWF. Our findings indicate that S1P-induced release of haemostatic, inflammatory and angiogenic components stored within WPBs depends on the S1PR3.","is_dataset_classified":null,"base_score":3.258096538021482,"endowment":3.258096538021482,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24632890","pmcid":"PMC3954688","openalex_id":"https://openalex.org/W2035941172","authors":[],"funders":[{"funder_name":"European Hematology Association","grant_id":"RG6","title":null}],"total_grants":1,"fwci":1.2997,"citation_percentile":0.78946978,"influential_citations":0,"citation_trend":[{"year":2015,"count":5},{"year":2016,"count":4},{"year":2017,"count":1},{"year":2018,"count":2},{"year":2019,"count":3},{"year":2020,"count":2},{"year":2021,"count":2},{"year":2022,"count":5},{"year":2024,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0091346&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0091346&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pone.0091346","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pone.0091346","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/24632890","host_type":"repository"},{"url":"https://pure.amsterdamumc.nl/en/publications/1f0b4a92-da56-4858-857a-5d12ba13888b","host_type":"repository"},{"url":"https://pure.amc.nl/en/publications/sphingosine1phosphate-receptor-3-mediates-sphingosine1phosphate-induced-release-of-weibelpalade-bodies-from-endothelial-cells(64956a79-daa2-47ac-a6b4-ea4efbe67e73).html","host_type":"repository"},{"url":"https://doaj.org/article/ecb94040bd484e56aacf2e23ee062e9c","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3954688","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC3954688","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC3954688?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Sphingolipid Metabolism and Signaling","Platelet Disorders and Treatments","Circadian rhythm and melatonin"],"mesh_terms":["Sphingosine-1-Phosphate Receptors","Amides","Cell Line","Enzyme Inhibitors","Humans","Protein Binding","Pyridines","Down-Regulation","Gene Expression","Weibel-Palade Bodies","Endothelial Cells","Receptors, Lysosphingolipid"],"keywords":["S1PR1","Sphingosine","Sphingosine-1-phosphate","Cell biology","Sphingosine-1-phosphate receptor","Exocytosis","Sphingosine kinase","Chemistry","RAC1","Endothelial stem cell","Receptor","Biology","Signal transduction","Biochemistry","Vascular endothelial growth factor A","Vascular endothelial growth factor","Secretion","Cancer research"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T20:39:42.771212Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}