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Impaired Sphingosine-1-Phosphate Synthesis Induces Preeclampsia by Deactivating Trophoblastic YAP (Yes-Associated Protein) Through S1PR2 (Sphingosine-1-Phosphate Receptor-2)-Induced Actin Polymerizations.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Impaired Sphingosine-1-Phosphate Synthesis Induces Preeclampsia by Deactivating Trophoblastic YAP (Yes-Associated Protein) Through S1PR2 (Sphingosine-1-Phosphate Receptor-2)-Induced Actin Polymerizations.
Συγγραφείς: Liao J; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.)., Zheng Y; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; Department of Stem Cell Transplantation and Cell Therapy, MD Anderson Cancer Center, Houston, TX (Y.Z.)., Hu M; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.)., Xu P; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.)., Lin L; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.)., Liu X; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.)., Wu Y; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.)., Huang B; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.)., Ye X; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.)., Li S; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.)., Duan R; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.)., Fu H; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.)., Huang J; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.)., Wen L; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.)., Fu Y; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.)., Kilby MD; Institute of Metabolism and System Research, College of Medical & Dental Sciences, University of Birmingham and the Fetal Medicine Centre, Birmingham Women's and Children's Foundation Trust, United Kingdom (M.D.K.)., Kenny LC; Department of Women's and Children's Health, Institute of Life Course and Medical Sciences, Faculty of Health and Life Sciences, University of Liverpool, United Kingdom (L.C.K.)., Baker PN; College of Life Sciences, University of Leicester, United Kingdom (P.N.B.)., Qi H; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; Chongqing Women and Children's Health Center, China (H.Q.)., Tong C; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).
Πηγή: Hypertension (Dallas, Tex. : 1979) [Hypertension] 2022 Feb; Vol. 79 (2), pp. 399-412. Date of Electronic Publication: 2021 Dec 06.
Τύπος έκδοσης: Journal Article; Research Support, Non-U.S. Gov't
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Lippincott, Williams & Wilkins Country of Publication: United States NLM ID: 7906255 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4563 (Electronic) Linking ISSN: 0194911X NLM ISO Abbreviation: Hypertension Subsets: MEDLINE
Imprint Name(s): Publication: : Hagerstown, MD : Lippincott, Williams & Wilkins
Original Publication: [Dallas, Tex.] : [American Heart Association], [©1979]-
Ιατρικοί όροι (MeSH): Actins/*metabolism , Lysophospholipids/*metabolism , Pre-Eclampsia/*metabolism , Proto-Oncogene Proteins c-yes/*metabolism , Sphingosine/*analogs & derivatives , Sphingosine-1-Phosphate Receptors/*metabolism , Trophoblasts/*metabolism, Lysophospholipids/genetics ; Placenta/metabolism ; Placentation/physiology ; Proto-Oncogene Proteins c-yes/genetics ; Signal Transduction/physiology ; Sphingosine/genetics ; Sphingosine/metabolism ; Sphingosine-1-Phosphate Receptors/genetics ; Animals ; Female ; Humans ; Mice ; Pregnancy
Περίληψη: Incomplete spiral artery remodeling, caused by impaired extravillous trophoblast invasion, is a fundamental pathogenic process associated with malplacentation and the development of preeclampsia. Nevertheless, the mechanisms controlling this regulation of trophoblast invasion are largely unknown. We report that sphingosine-1-phosphate synthesis and expression is abundant in healthy trophoblast, whereas in pregnancies complicated by preeclampsia the placentae are associated with reduced sphingosine-1-phosphate and lower SPHK1 (sphingosine kinase 1) expression and activity. In vivo inhibition of sphingosine kinase 1 activity during placentation in pregnant mice led to decreased placental sphingosine-1-phosphate production and defective placentation, resulting in a preeclampsia phenotype. Moreover, sphingosine-1-phosphate increased HTR8/SVneo (immortalized human trophoblst cells) cell invasion in a Hippo-signaling-dependent transcriptional coactivator YAP (Yes-associated protein) dependent manner, which is activated by S1PR2 (sphingosine-1-phosphate receptor-2) and downstream RhoA (Ras homolog gene family, member A)/ROCK (Rho-associated protein kinase) induced actin polymerization. Mutation-based YAP-5SA (S61A, S109A, S127A, S164A, S381A) demonstrated that sphingosine-1-phosphate activation of YAP could be either dependent or independent of Hippo signaling. Together, these findings suggest a novel pathogenic pathway of preeclampsia via disrupted sphingosine-1-phosphate metabolism and signaling-induced, interrupted actin dynamics and YAP deactivation; this may lead to potential novel intervention targets for the prevention and management of preeclampsia.
Contributed Indexing: Keywords: cytoskeleton; preeclampsia; pregnancy; sphingosine; trophoblasts
Substance Nomenclature: 0 (Actins)
0 (Lysophospholipids)
0 (Sphingosine-1-Phosphate Receptors)
0 (sphingosine-1-phosphate receptor-2, mouse)
26993-30-6 (sphingosine 1-phosphate)
EC 2.7.10.2 (Proto-Oncogene Proteins c-yes)
EC 2.7.10.2 (Yes1 protein, mouse)
NGZ37HRE42 (Sphingosine)
Entry Date(s): Date Created: 20211206 Date Completed: 20220228 Latest Revision: 20220228
Update Code: 20260130
DOI: 10.1161/HYPERTENSIONAHA.121.18363
PMID: 34865521
Βάση Δεδομένων: MEDLINE
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Header DbId: cmedm
DbLabel: MEDLINE
An: 34865521
AccessLevel: 3
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
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Items – Name: Title
  Label: Title
  Group: Ti
  Data: Impaired Sphingosine-1-Phosphate Synthesis Induces Preeclampsia by Deactivating Trophoblastic YAP (Yes-Associated Protein) Through S1PR2 (Sphingosine-1-Phosphate Receptor-2)-Induced Actin Polymerizations.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AU" term="%22Liao+J%22">Liao J</searchLink>; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).<br /><searchLink fieldCode="AU" term="%22Zheng+Y%22">Zheng Y</searchLink>; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; Department of Stem Cell Transplantation and Cell Therapy, MD Anderson Cancer Center, Houston, TX (Y.Z.).<br /><searchLink fieldCode="AU" term="%22Hu+M%22">Hu M</searchLink>; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).<br /><searchLink fieldCode="AU" term="%22Xu+P%22">Xu P</searchLink>; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).<br /><searchLink fieldCode="AU" term="%22Lin+L%22">Lin L</searchLink>; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).<br /><searchLink fieldCode="AU" term="%22Liu+X%22">Liu X</searchLink>; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).<br /><searchLink fieldCode="AU" term="%22Wu+Y%22">Wu Y</searchLink>; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).<br /><searchLink fieldCode="AU" term="%22Huang+B%22">Huang B</searchLink>; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).<br /><searchLink fieldCode="AU" term="%22Ye+X%22">Ye X</searchLink>; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).<br /><searchLink fieldCode="AU" term="%22Li+S%22">Li S</searchLink>; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).<br /><searchLink fieldCode="AU" term="%22Duan+R%22">Duan R</searchLink>; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).<br /><searchLink fieldCode="AU" term="%22Fu+H%22">Fu H</searchLink>; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).<br /><searchLink fieldCode="AU" term="%22Huang+J%22">Huang J</searchLink>; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).<br /><searchLink fieldCode="AU" term="%22Wen+L%22">Wen L</searchLink>; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).<br /><searchLink fieldCode="AU" term="%22Fu+Y%22">Fu Y</searchLink>; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).<br /><searchLink fieldCode="AU" term="%22Kilby+MD%22">Kilby MD</searchLink>; Institute of Metabolism and System Research, College of Medical & Dental Sciences, University of Birmingham and the Fetal Medicine Centre, Birmingham Women's and Children's Foundation Trust, United Kingdom (M.D.K.).<br /><searchLink fieldCode="AU" term="%22Kenny+LC%22">Kenny LC</searchLink>; Department of Women's and Children's Health, Institute of Life Course and Medical Sciences, Faculty of Health and Life Sciences, University of Liverpool, United Kingdom (L.C.K.).<br /><searchLink fieldCode="AU" term="%22Baker+PN%22">Baker PN</searchLink>; College of Life Sciences, University of Leicester, United Kingdom (P.N.B.).<br /><searchLink fieldCode="AU" term="%22Qi+H%22">Qi H</searchLink>; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; Chongqing Women and Children's Health Center, China (H.Q.).<br /><searchLink fieldCode="AU" term="%22Tong+C%22">Tong C</searchLink>; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, China (J.L., Y.Z., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, China (J.L., M.H., P.X., L.L., X.L., Y.W., B.H., X.Y., S.L., R.D., H.F., J.H., L.W., Y.F., H.Q., C.T.).
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%227906255%22">Hypertension (Dallas, Tex. : 1979)</searchLink> [Hypertension] 2022 Feb; Vol. 79 (2), pp. 399-412. <i>Date of Electronic Publication: </i>2021 Dec 06.
– Name: TypePub
  Label: Publication Type
  Group: TypPub
  Data: Journal Article; Research Support, Non-U.S. Gov't
– Name: Language
  Label: Language
  Group: Lang
  Data: English
– Name: TitleSource
  Label: Journal Info
  Group: Src
  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Lippincott%2C+Williams+%26+Wilkins%22">Lippincott, Williams & Wilkins </searchLink><i>Country of Publication: </i>United States <i>NLM ID: </i>7906255 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1524-4563 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%220194911X%22">0194911X </searchLink><i>NLM ISO Abbreviation: </i>Hypertension <i>Subsets: </i>MEDLINE
– Name: PublisherInfo
  Label: Imprint Name(s)
  Group: PubInfo
  Data: <i>Publication</i>: <Jan. 2002- > : Hagerstown, MD : Lippincott, Williams & Wilkins<br /><i>Original Publication</i>: [Dallas, Tex.] : [American Heart Association], [©1979]-
– Name: SubjectMESH
  Label: MeSH Terms
  Group: Su
  Data: <searchLink fieldCode="MM" term="%22Actins%22">Actins</searchLink>/<searchLink fieldCode="MM" term="%22Actins+metabolism%22">*metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Lysophospholipids%22">Lysophospholipids</searchLink>/<searchLink fieldCode="MM" term="%22Lysophospholipids+metabolism%22">*metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Pre-Eclampsia%22">Pre-Eclampsia</searchLink>/<searchLink fieldCode="MM" term="%22Pre-Eclampsia+metabolism%22">*metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Proto-Oncogene+Proteins+c-yes%22">Proto-Oncogene Proteins c-yes</searchLink>/<searchLink fieldCode="MM" term="%22Proto-Oncogene+Proteins+c-yes+metabolism%22">*metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Sphingosine%22">Sphingosine</searchLink>/<searchLink fieldCode="MM" term="%22Sphingosine+analogs+%26+derivatives%22">*analogs & derivatives</searchLink> <br /><searchLink fieldCode="MM" term="%22Sphingosine-1-Phosphate+Receptors%22">Sphingosine-1-Phosphate Receptors</searchLink>/<searchLink fieldCode="MM" term="%22Sphingosine-1-Phosphate+Receptors+metabolism%22">*metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Trophoblasts%22">Trophoblasts</searchLink>/<searchLink fieldCode="MM" term="%22Trophoblasts+metabolism%22">*metabolism</searchLink><br /><searchLink fieldCode="MH" term="%22Lysophospholipids%22">Lysophospholipids</searchLink>/<searchLink fieldCode="MH" term="%22Lysophospholipids+genetics%22">genetics</searchLink> ; <searchLink fieldCode="MH" term="%22Placenta%22">Placenta</searchLink>/<searchLink fieldCode="MH" term="%22Placenta+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Placentation%22">Placentation</searchLink>/<searchLink fieldCode="MH" term="%22Placentation+physiology%22">physiology</searchLink> ; <searchLink fieldCode="MH" term="%22Proto-Oncogene+Proteins+c-yes%22">Proto-Oncogene Proteins c-yes</searchLink>/<searchLink fieldCode="MH" term="%22Proto-Oncogene+Proteins+c-yes+genetics%22">genetics</searchLink> ; <searchLink fieldCode="MH" term="%22Signal+Transduction%22">Signal Transduction</searchLink>/<searchLink fieldCode="MH" term="%22Signal+Transduction+physiology%22">physiology</searchLink> ; <searchLink fieldCode="MH" term="%22Sphingosine%22">Sphingosine</searchLink>/<searchLink fieldCode="MH" term="%22Sphingosine+genetics%22">genetics</searchLink> ; <searchLink fieldCode="MH" term="%22Sphingosine%22">Sphingosine</searchLink>/<searchLink fieldCode="MH" term="%22Sphingosine+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Sphingosine-1-Phosphate+Receptors%22">Sphingosine-1-Phosphate Receptors</searchLink>/<searchLink fieldCode="MH" term="%22Sphingosine-1-Phosphate+Receptors+genetics%22">genetics</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Female%22">Female</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%22">Mice</searchLink> ; <searchLink fieldCode="MH" term="%22Pregnancy%22">Pregnancy</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Incomplete spiral artery remodeling, caused by impaired extravillous trophoblast invasion, is a fundamental pathogenic process associated with malplacentation and the development of preeclampsia. Nevertheless, the mechanisms controlling this regulation of trophoblast invasion are largely unknown. We report that sphingosine-1-phosphate synthesis and expression is abundant in healthy trophoblast, whereas in pregnancies complicated by preeclampsia the placentae are associated with reduced sphingosine-1-phosphate and lower SPHK1 (sphingosine kinase 1) expression and activity. In vivo inhibition of sphingosine kinase 1 activity during placentation in pregnant mice led to decreased placental sphingosine-1-phosphate production and defective placentation, resulting in a preeclampsia phenotype. Moreover, sphingosine-1-phosphate increased HTR8/SVneo (immortalized human trophoblst cells) cell invasion in a Hippo-signaling-dependent transcriptional coactivator YAP (Yes-associated protein) dependent manner, which is activated by S1PR2 (sphingosine-1-phosphate receptor-2) and downstream RhoA (Ras homolog gene family, member A)/ROCK (Rho-associated protein kinase) induced actin polymerization. Mutation-based YAP-5SA (S61A, S109A, S127A, S164A, S381A) demonstrated that sphingosine-1-phosphate activation of YAP could be either dependent or independent of Hippo signaling. Together, these findings suggest a novel pathogenic pathway of preeclampsia via disrupted sphingosine-1-phosphate metabolism and signaling-induced, interrupted actin dynamics and YAP deactivation; this may lead to potential novel intervention targets for the prevention and management of preeclampsia.
– Name: SubjectMinor
  Label: Contributed Indexing
  Group:
  Data: <i>Keywords: </i>cytoskeleton; preeclampsia; pregnancy; sphingosine; trophoblasts
– Name: NumberCAS
  Label: Substance Nomenclature
  Group: ID
  Data: 0 (Actins)<br />0 (Lysophospholipids)<br />0 (Sphingosine-1-Phosphate Receptors)<br />0 (sphingosine-1-phosphate receptor-2, mouse)<br />26993-30-6 (sphingosine 1-phosphate)<br />EC 2.7.10.2 (Proto-Oncogene Proteins c-yes)<br />EC 2.7.10.2 (Yes1 protein, mouse)<br />NGZ37HRE42 (Sphingosine)
– Name: DateEntry
  Label: Entry Date(s)
  Group: Date
  Data: <i>Date Created: </i>20211206 <i>Date Completed: </i>20220228 <i>Latest Revision: </i>20220228
– Name: DateUpdate
  Label: Update Code
  Group: Date
  Data: 20260130
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1161/HYPERTENSIONAHA.121.18363
– Name: AN
  Label: PMID
  Group: ID
  Data: 34865521
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=34865521
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1161/HYPERTENSIONAHA.121.18363
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 399
    Subjects:
      – SubjectFull: Lysophospholipids genetics
        Type: general
      – SubjectFull: Placenta metabolism
        Type: general
      – SubjectFull: Placentation physiology
        Type: general
      – SubjectFull: Proto-Oncogene Proteins c-yes genetics
        Type: general
      – SubjectFull: Signal Transduction physiology
        Type: general
      – SubjectFull: Sphingosine genetics
        Type: general
      – SubjectFull: Sphingosine metabolism
        Type: general
      – SubjectFull: Sphingosine-1-Phosphate Receptors genetics
        Type: general
      – SubjectFull: Animals
        Type: general
      – SubjectFull: Female
        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Mice
        Type: general
      – SubjectFull: Pregnancy
        Type: general
      – SubjectFull: Actins metabolism
        Type: general
      – SubjectFull: Lysophospholipids metabolism
        Type: general
      – SubjectFull: Pre-Eclampsia metabolism
        Type: general
      – SubjectFull: Proto-Oncogene Proteins c-yes metabolism
        Type: general
      – SubjectFull: Sphingosine analogs & derivatives
        Type: general
      – SubjectFull: Sphingosine-1-Phosphate Receptors metabolism
        Type: general
      – SubjectFull: Trophoblasts metabolism
        Type: general
    Titles:
      – TitleFull: Impaired Sphingosine-1-Phosphate Synthesis Induces Preeclampsia by Deactivating Trophoblastic YAP (Yes-Associated Protein) Through S1PR2 (Sphingosine-1-Phosphate Receptor-2)-Induced Actin Polymerizations.
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              Text: 2022 Feb
              Type: published
              Y: 2022
          Identifiers:
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          Titles:
            – TitleFull: Hypertension (Dallas, Tex. : 1979)
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