Evidence mapPaperPMID 41560531Full record

ArticleJournal of cellular physiology2026

Blocking Sphingosine 1-phosphate Metabolism With Fingolimod Prevents the Progression of Vascular Smooth Muscle Cells Calcification in Chronic Kidney Disease.

Najwa Skafi, Solenne Pelletier, Christophe O Soulage, Sarah Nahle, Beatriz O Da Cruz, Rayan Othmani, Anne Briolay, Sophie Reibel, Nicolas Vitale, Eva Hamade and 7 more

Erratum issuedAbstract read
In one paragraph

Article in Journal of cellular physiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Najwa SkafiUniv Lyon, Universite Claude Bernard Lyon 1, UMR CNRS 5246, ICBMS, Lyon, France.
Solenne PelletierDépartement de Néphrologie-Dialyse-Nutrition, Centre Hôpital Lyon Sud, Univ Lyon, UCBL, Inserm 1033, Pierre Bénite, France.
Christophe O SoulageCarMeN Lab, INSERM U1060, INRA U1397, Universite Claude Bernard Lyon 1, Bron, France.
Sarah NahleUniversite Jean Monnet Saint-Étienne, INSERM, Mines Saint Etienne, Saint-Étienne, France.
Beatriz O Da CruzCardiovascular Sciences Graduation Program, Fluminense Federal University (UFF), Niterói, Brazil.
Rayan OthmaniUniv Lyon, Universite Claude Bernard Lyon 1, UMR CNRS 5246, ICBMS, Lyon, France.
Anne BriolayUniv Lyon, Universite Claude Bernard Lyon 1, UMR CNRS 5246, ICBMS, Lyon, France.
Sophie ReibelChronobiotron UAR3415, Strasbourg, France.
Nicolas VitaleInstitut des Neurosciences Cellulaires et Intégratives (INCI), UPR-3212 CNRS and Université de Strasbourg, 8 Allée du Général Rouvillois, Strasbourg, France.
Eva HamadeGenomic and Health Laboratory/PRASE-EDST Campus Rafic Hariri-Hadath-Beirut-Liban, Faculty of Sciences, Lebanese University, Beirut, Lebanon.
Bassan BadranGenomic and Health Laboratory/PRASE-EDST Campus Rafic Hariri-Hadath-Beirut-Liban, Faculty of Sciences, Lebanese University, Beirut, Lebanon.
David MagneUniv Lyon, Universite Claude Bernard Lyon 1, UMR CNRS 5246, ICBMS, Lyon, France.
Rene BuchetUniv Lyon, Universite Claude Bernard Lyon 1, UMR CNRS 5246, ICBMS, Lyon, France.ORCID 0000-0002-7966-3856
Milena B Stockler-PintoCardiovascular Sciences Graduation Program, Fluminense Federal University (UFF), Niterói, Brazil.ORCID 0000-0003-0131-2033
Denis FouqueDépartement de Néphrologie-Dialyse-Nutrition, Centre Hôpitalier Lyon Sud, Univ Lyon, UCBL, CARMEN, CENS, Pierre Bénite, France.
Saida MebarekUniv Lyon, Universite Claude Bernard Lyon 1, UMR CNRS 5246, ICBMS, Lyon, France.
Leyre BrizuelaUniv Lyon, Universite Claude Bernard Lyon 1, UMR CNRS 5246, ICBMS, Lyon, France.ORCID 0000-0001-5227-8811

Funding

Societé Francophone de Néphrologie, Dialyse et Transplantation (SFNDT) [IRC terminale: 2021, 2024]Université Claude Bernard Lyon 1: Bourse Qualité Recherche 2014
6 · The paper itself

Abstract

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-phosphate is a pleiotropic sphingolipid and an important regulator of osteogenesis and the cardiovascular system. Therefore, we explored the role of sphingosine 1-phosphate metabolism in chronic kidney disease-derived vascular calcification. Vascular calcification progression in chronic kidney disease and sphingosine 1-phosphate signaling were examined in calcified vascular smooth muscle cells, in aortic explants, in rats with adenine-induced chronic kidney disease, as well as in serum from hemodialysis patients. Sphingosine kinase 2 activity and sphingosine 1-phosphate 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-phosphate, supporting intertwined signalization cascades. Overall, sphingosine kinase expression and activity were upregulated in calcified aortic explants and in calcified aortas from rats. Sphingosine 1-phosphate was increased in the serum of rats with mild vascular calcification. The Food and Drug Administration-approved 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-phosphate was significantly increased in hemodialysis patients with mild abdominal aortic calcification. Our findings open an unexplored therapeutic option, which is targeting sphingosine 1-phosphate metabolism, eventually with fingolimod, for the prevention and treatment of vascular calcification in chronic kidney disease patients.

Indexed as

Fingolimod HydrochlorideLysophospholipidsMuscle, Smooth, VascularMyocytes, Smooth MuscleRenal Insufficiency, ChronicSphingosineSphingosine 1 Phosphate Receptor ModulatorsVascular CalcificationAnimalsAortaDisease ProgressionHumansMaleMiceMice, KnockoutPhosphotransferases (Alcohol Group Acceptor)Fingolimod HydrochlorideLysophospholipidsPhosphotransferases (Alcohol Group Acceptor)Sphingosinesphingosine 1-phosphateSphingosine 1 Phosphate Receptor ModulatorsSphingosine Kinasechronic kidney diseasefingolimodSphingosine 1‐phosphatevascular calcificationvascular smooth muscle cells

Identifiers

PMID41560531
PMCPMC12820537

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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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 Socratic graph.