{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:24:24Z","timestamp":1791944664832,"version":"4.3.4"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Patients with chronic kidney disease, and particularly those under hemodialysis, are prone to develop cardiovascular complications, mostly due to the exacerbation of vascular calcification. Vascular calcification relies on the transdifferentiation of vascular smooth muscle cells into calcifying cells. Sphingosine 1\u2010phosphate is a pleiotropic sphingolipid and an important regulator of osteogenesis and the cardiovascular system. Therefore, we explored the role of sphingosine 1\u2010phosphate metabolism in chronic kidney disease\u2010derived vascular calcification. Vascular calcification progression in chronic kidney disease and sphingosine 1\u2010phosphate signaling were examined in calcified vascular smooth muscle cells, in aortic explants, in rats with adenine\u2010induced chronic kidney disease, as well as in serum from hemodialysis patients. Sphingosine kinase 2 activity and sphingosine 1\u2010phosphate secretion, under the control of phospholipase D1, were exacerbated in calcified vascular smooth muscle cells. Furthermore, phospholipase D1 knockout mice display significantly less circulating sphingosine 1\u2010phosphate, supporting intertwined signalization cascades. Overall, sphingosine kinase expression and activity were upregulated in calcified aortic explants and in calcified aortas from rats. Sphingosine 1\u2010phosphate was increased in the serum of rats with mild vascular calcification. The Food and Drug Administration\u2010approved immunosuppressant drug fingolimod, a general modulator of S1P metabolism, strongly inhibited calcification in vascular smooth muscle cells and aortic explants. Additionally, fingolimod significantly reduced inflammation, attenuated metabolic syndrome and moderately inhibited aortic calcification in rats. Finally, we demonstrated for the first time that serum sphingosine 1\u2010phosphate was significantly increased in hemodialysis patients with mild abdominal aortic calcification. Our findings open an unexplored therapeutic option, which is targeting sphingosine 1\u2010phosphate metabolism, eventually with fingolimod, for the prevention and treatment of vascular calcification in chronic kidney disease patients.<\/jats:p>","DOI":"10.1002\/jcp.70137","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T08:13:59Z","timestamp":1768983239000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Blocking Sphingosine 1\u2010phosphate Metabolism With Fingolimod Prevents the Progression of Vascular Smooth Muscle Cells Calcification in Chronic Kidney Disease"],"prefix":"10.1002","volume":"241","author":[{"given":"Najwa","family":"Skafi","sequence":"first","affiliation":[{"name":"Univ Lyon, Universite Claude Bernard Lyon 1, UMR CNRS 5246, ICBMS Lyon France"},{"name":"Genomic and Health Laboratory\/PRASE\u2010EDST Campus Rafic Hariri\u2010Hadath\u2010Beirut\u2010Liban, Faculty of Sciences Lebanese University Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solenne","family":"Pelletier","sequence":"additional","affiliation":[{"name":"D\u00e9partement de N\u00e9phrologie\u2010Dialyse\u2010Nutrition, Centre H\u00f4pital Lyon Sud Univ Lyon, UCBL, Inserm 1033 Pierre B\u00e9nite France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe O.","family":"Soulage","sequence":"additional","affiliation":[{"name":"CarMeN Lab INSERM U1060, INRA U1397, Universite Claude Bernard Lyon 1 Bron France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Nahle","sequence":"additional","affiliation":[{"name":"Universite Jean Monnet Saint\u2010E\u0301tienne, INSERM, Mines Saint Etienne Saint\u2010E\u0301tienne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz O.","family":"Da Cruz","sequence":"additional","affiliation":[{"name":"Cardiovascular Sciences Graduation Program Fluminense Federal University (UFF) Niter\u00f3i Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayan","family":"Othmani","sequence":"additional","affiliation":[{"name":"Univ Lyon, Universite Claude Bernard Lyon 1, UMR CNRS 5246, ICBMS Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Briolay","sequence":"additional","affiliation":[{"name":"Univ Lyon, Universite Claude Bernard Lyon 1, UMR CNRS 5246, ICBMS Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Reibel","sequence":"additional","affiliation":[{"name":"Chronobiotron UAR3415 Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Vitale","sequence":"additional","affiliation":[{"name":"Institut des Neurosciences Cellulaires et Int\u00e9gratives (INCI) UPR\u20103212 CNRS and Universit\u00e9 de Strasbourg, 8 All\u00e9e du G\u00e9n\u00e9ral Rouvillois Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Hamade","sequence":"additional","affiliation":[{"name":"Genomic and Health Laboratory\/PRASE\u2010EDST Campus Rafic Hariri\u2010Hadath\u2010Beirut\u2010Liban, Faculty of Sciences Lebanese University Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bassan","family":"Badran","sequence":"additional","affiliation":[{"name":"Genomic and Health Laboratory\/PRASE\u2010EDST Campus Rafic Hariri\u2010Hadath\u2010Beirut\u2010Liban, Faculty of Sciences Lebanese University Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Magne","sequence":"additional","affiliation":[{"name":"Univ Lyon, Universite Claude Bernard Lyon 1, UMR CNRS 5246, ICBMS Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7966-3856","authenticated-orcid":false,"given":"Rene","family":"Buchet","sequence":"additional","affiliation":[{"name":"Univ Lyon, Universite Claude Bernard Lyon 1, UMR CNRS 5246, ICBMS Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0131-2033","authenticated-orcid":false,"given":"Milena B.","family":"Stockler\u2010Pinto","sequence":"additional","affiliation":[{"name":"Cardiovascular Sciences Graduation Program Fluminense Federal University (UFF) Niter\u00f3i Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Fouque","sequence":"additional","affiliation":[{"name":"D\u00e9partement de N\u00e9phrologie\u2010Dialyse\u2010Nutrition, Centre H\u00f4pitalier Lyon Sud Univ Lyon, UCBL, CARMEN, CENS Pierre B\u00e9nite France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saida","family":"Mebarek","sequence":"additional","affiliation":[{"name":"Univ Lyon, Universite Claude Bernard Lyon 1, UMR CNRS 5246, ICBMS Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5227-8811","authenticated-orcid":false,"given":"Leyre","family":"Brizuela","sequence":"additional","affiliation":[{"name":"Univ Lyon, Universite Claude Bernard Lyon 1, UMR CNRS 5246, ICBMS Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9070804"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.067270"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-020-03827-2"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2017.07.002"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/oncsis.2016.13"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200176200"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10-160838"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22062948"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/8571649"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2022.2138330"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/381800a0"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2023.2178898"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2018.07.010"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2011.07.021"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2000551"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.12.003"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0109081"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24086935"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.107"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21062204"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2019.115087"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3844"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14092183"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0021-9150(97)00106-8"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082379"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfg414"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20201122"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1070238"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008070692"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-50621-6_10"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M079731"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom14030275"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-1388"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-015-3127-9"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.07670712"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-800-9_2"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-025-03068-6"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M093799"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62956"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.S091181"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfae431"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-024-03029-5"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25053024"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27281"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.S091959"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.122.317332"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2022.116506"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2010.03.428"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvs002"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12897"}],"updated-by":[{"DOI":"10.1002\/jcp.70149","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000}}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.70137","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcp.70137","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.70137","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T07:31:48Z","timestamp":1776238308000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.70137"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/jcp.70137"],"URL":"https:\/\/doi.org\/10.1002\/jcp.70137","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-08-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70137"}}