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

Thanh Nha Uyen Le; Toan Q. Nguyen; Pazhanichamy Kalailingam; Yen Thi Kim Nguyen; Viresh Krishnan Sukumar; Clarissa Kai Hui Tan; Farhana Tukijan; Ludovic Couty; Zafrul Hasan; Ilaria Del Gaudio; Markus R. Wenk; Amaury Cazenave-Gassiot; Eric Camerer; Long N. Nguyen

doi:10.1016/j.celrep.2022.111208

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

Thanh Nha Uyen Le, Toan Q. Nguyen, Pazhanichamy Kalailingam, Yen Thi Kim Nguyen, Viresh Krishnan Sukumar, Clarissa Kai Hui Tan, Farhana Tukijan, Ludovic Couty, Zafrul Hasan, Ilaria Del Gaudio, Markus R. Wenk, Amaury Cazenave-Gassiot, Eric Camerer, Long N. Nguyen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

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.

Original language	English
Article number	111208
Journal	Cell Reports
Volume	40
Issue number	7
DOIs	https://doi.org/10.1016/j.celrep.2022.111208
Publication status	Published - 16 Aug 2022
Externally published	Yes

Keywords

CP: Developmental biology
CP: Molecular biology
Mfsd2b
S1P signaling
S1P transporters
Spns2
anaphylaxis
embryonic lethality
hemorrhage
plasma S1P
sphingolipids
sphingosine kinases
sphingosine-1-phosphate
vascular homeostasis

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10.1016/j.celrep.2022.111208

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Le, T. N. U., Nguyen, T. Q., Kalailingam, P., Nguyen, Y. T. K., Sukumar, V. K., Tan, C. K. H., Tukijan, F., Couty, L., Hasan, Z., Del Gaudio, I., Wenk, M. R., Cazenave-Gassiot, A., Camerer, E., & Nguyen, L. N. (2022). Mfsd2b and Spns2 are essential for maintenance of blood vessels during development and in anaphylactic shock. Cell Reports, 40(7), Article 111208. https://doi.org/10.1016/j.celrep.2022.111208

@article{5c43c72c8f294af7889a6cdfe16aec5c,

title = "Mfsd2b and Spns2 are essential for maintenance of blood vessels during development and in anaphylactic shock",

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.",

keywords = "CP: Developmental biology, CP: Molecular biology, Mfsd2b, S1P signaling, S1P transporters, Spns2, anaphylaxis, embryonic lethality, hemorrhage, plasma S1P, sphingolipids, sphingosine kinases, sphingosine-1-phosphate, vascular homeostasis",

author = "Le, {Thanh Nha Uyen} and Nguyen, {Toan Q.} and Pazhanichamy Kalailingam and Nguyen, {Yen Thi Kim} and Sukumar, {Viresh Krishnan} and Tan, {Clarissa Kai Hui} and Farhana Tukijan and Ludovic Couty and Zafrul Hasan and {Del Gaudio}, Ilaria and Wenk, {Markus R.} and Amaury Cazenave-Gassiot and Eric Camerer and Nguyen, {Long N.}",

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = aug,

day = "16",

doi = "10.1016/j.celrep.2022.111208",

language = "English",

volume = "40",

journal = "Cell Reports",

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Le, TNU, Nguyen, TQ, Kalailingam, P, Nguyen, YTK, Sukumar, VK, Tan, CKH, Tukijan, F, Couty, L, Hasan, Z, Del Gaudio, I, Wenk, MR, Cazenave-Gassiot, A, Camerer, E & Nguyen, LN 2022, 'Mfsd2b and Spns2 are essential for maintenance of blood vessels during development and in anaphylactic shock', Cell Reports, vol. 40, no. 7, 111208. https://doi.org/10.1016/j.celrep.2022.111208

TY - JOUR

T1 - Mfsd2b and Spns2 are essential for maintenance of blood vessels during development and in anaphylactic shock

AU - Le, Thanh Nha Uyen

AU - Nguyen, Toan Q.

AU - Kalailingam, Pazhanichamy

AU - Nguyen, Yen Thi Kim

AU - Sukumar, Viresh Krishnan

AU - Tan, Clarissa Kai Hui

AU - Tukijan, Farhana

AU - Couty, Ludovic

AU - Hasan, Zafrul

AU - Del Gaudio, Ilaria

AU - Wenk, Markus R.

AU - Cazenave-Gassiot, Amaury

AU - Camerer, Eric

AU - Nguyen, Long N.

PY - 2022/8/16

Y1 - 2022/8/16

N2 - 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.

AB - 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.

KW - CP: Developmental biology

KW - CP: Molecular biology

KW - Mfsd2b

KW - S1P signaling

KW - S1P transporters

KW - Spns2

KW - anaphylaxis

KW - embryonic lethality

KW - hemorrhage

KW - plasma S1P

KW - sphingolipids

KW - sphingosine kinases

KW - sphingosine-1-phosphate

KW - vascular homeostasis

UR - http://www.scopus.com/inward/record.url?scp=85135914916&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2022.111208

DO - 10.1016/j.celrep.2022.111208

M3 - Article

C2 - 35977478

AN - SCOPUS:85135914916

SN - 2211-1247

VL - 40

JO - Cell Reports

JF - Cell Reports

IS - 7

M1 - 111208

ER -

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

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Keywords

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