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

Autor:	Le TNU; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore., Nguyen TQ; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore., Kalailingam P; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore., Nguyen YTK; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore., Sukumar VK; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore., Tan CKH; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore., Tukijan F; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore., Couty L; Université Paris Cité, PARCC, INSERM U970, 56 Rue Leblanc, 75015 Paris, France., Hasan Z; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore., Del Gaudio I; Université Paris Cité, PARCC, INSERM U970, 56 Rue Leblanc, 75015 Paris, France., Wenk MR; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore; Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore., Cazenave-Gassiot A; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore; Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore., Camerer E; Université Paris Cité, PARCC, INSERM U970, 56 Rue Leblanc, 75015 Paris, France., Nguyen LN; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore; Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore; Cardiovascular Disease Research (CVD) Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore; Immunology Program, Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore; Immunology Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore. Electronic address: bchnnl@nus.edu.sg.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Aug 16; Vol. 40 (7), pp. 111208.
DOI:	10.1016/j.celrep.2022.111208
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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