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Article Dans Une Revue Cell Reports Année : 2022

Mfsd2b and Spns2 are essential for maintenance of blood vessels during development and in anaphylactic shock

Thanh Nha Uyen Le
  • Fonction : Auteur
Toan Q Nguyen
Pazhanichamy Kalailingam
  • Fonction : Auteur
Yen Thi Kim Nguyen
  • Fonction : Auteur
Viresh Krishnan Sukumar
  • Fonction : Auteur
Clarissa Kai Hui Tan
  • Fonction : Auteur
Farhana Tukijan
  • Fonction : Auteur
Zafrul Hasan
Ilaria del Gaudio
  • Fonction : Auteur
Markus R Wenk
  • Fonction : Auteur
Amaury Cazenave-Gassiot
Eric Camerer
Long N Nguyen

Résumé

Sphingosine-1-phosphate (S1P) is a potent lipid mediator that is secreted by several cell types. We recently showed that Mfsd2b is an S1P transporter from hematopoietic cells that contributes approximately 50% plasma S1P. Here we report the characterization of compound deletion of Mfsd2b and Spns2, another S1P transporter active primarily in endothelial cells. Global deletion of Mfsd2b and Spns2 (global double knockout [gDKO]) results in embryonic lethality beyond embryonic day 14.5 (E14.5), with severe hemorrhage accompanied by defects of tight junction proteins, indicating that Mfsd2b and Spns2 provide S1P for signaling, which is essential for blood vessel integrity. Compound postnatal deletion of Mfsd2b and Spns2 using Mx1Cre (ctDKO-Mx1Cre) results in maximal 80% reduction of plasma S1P. ctDKO-Mx1Cre mice exhibit severe susceptibility to anaphylaxis, indicating that S1P from Mfsd2b and Spns2 is indispensable for vascular homeostasis. Our results show that S1P export from Mfsd2b and Spns2 is essential for developing and mature vasculature.
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hal-03885600 , version 1 (05-12-2022)

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Thanh Nha Uyen Le, Toan Q Nguyen, Pazhanichamy Kalailingam, Yen Thi Kim Nguyen, Viresh Krishnan Sukumar, et al.. Mfsd2b and Spns2 are essential for maintenance of blood vessels during development and in anaphylactic shock. Cell Reports, 2022, 40 (7), pp.111208. ⟨10.1016/j.celrep.2022.111208⟩. ⟨hal-03885600⟩

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