Mfsd2b and Spns2 are essential for maintenance of blood vessels during development and in anaphylactic shock - Université Paris Cité Access content directly
Journal Articles Cell Reports Year : 2022

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

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

Abstract

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.
Fichier principal
Vignette du fichier
Cell Reports 2022.pdf (6.8 Mo) Télécharger le fichier
Origin : Publisher files allowed on an open archive

Dates and versions

hal-03885600 , version 1 (05-12-2022)

Identifiers

Cite

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⟩

Collections

UP-SANTE ANR
0 View
13 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More