A Single Sphingomyelin Species Promotes Exosomal Release of Endoglin into the Maternal Circulation in Preeclampsia

被引：60
作者：
Ermini, Leonardo [1 ]
Ausman, Jonathan [3 ,4 ]
Melland-Smith, Megan [3 ,6 ]
Yeganeh, Behzad [1 ]
Rolfo, Alessandro [3 ]
Litvack, Michael L. [1 ]
Todros, Tullia [9 ]
Letarte, Michelle [2 ,8 ]
Post, Martin [1 ,4 ,6 ,7 ]
Caniggia, Isabella [3 ,4 ,5 ,6 ]
机构：
[1] Hosp Sick Children, Program Translat Med, Toronto, ON M5G 1X8, Canada
[2] Hosp Sick Children, Program Mol Med, Toronto, ON M5G 1X8, Canada
[3] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada
[4] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada
[5] Univ Toronto, Dept Obstet & Gynecol, Toronto, ON M5S 1A8, Canada
[6] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada
[7] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada
[8] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada
[9] Univ Turin, Dept Obstet & Gynecol, I-10126 Turin, Italy
来源：
SCIENTIFIC REPORTS | 2017年 / 7卷
基金：
加拿大健康研究院; 美国国家卫生研究院;
关键词：
TYROSINE KINASE 1; SPHINGOLIPID METABOLISM; SOLUBLE ENDOGLIN; LIPID RAFTS; MATRIX; METALLOPROTEINASE; PROTEINS; PREGNANCIES; MEMBRANES; BINDING;
D O I：
10.1038/s41598-017-12491-4
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Preeclampsia (PE), an hypertensive disorder of pregnancy, exhibits increased circulating levels of a short form of the auxillary TGF-beta (TGFB) receptor endoglin (sENG). Until now, its release and functionality in PE remains poorly understood. Here we show that ENG selectively interacts with sphingomyelin(SM)-18:0 which promotes its clustering with metalloproteinase 14 (MMP14) in SM-18:0 enriched lipid rafts of the apical syncytial membranes from PE placenta where ENG is cleaved by MMP14 into sENG. The SM-18: 0 enriched lipid rafts also contain type 1 and 2 TGFB receptors (TGFBR1 and TGFBR2), but not soluble fms-like tyrosine kinase 1 (sFLT1), another protein secreted in excess in the circulation of women with PE. The truncated ENG is then released into the maternal circulation via SM-18: 0 enriched exosomes together with TGFBR1 and 2. Such an exosomal TGFB receptor complex could be functionally active and block the vascular effects of TGFB in the circulation of PE women.
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页数：16
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