title: Thrombin enhances soluble Fms-like tyrosine kinase 1 expression in trophoblasts; possible involvement in the pathogenesis of preeclampsia.
abstract: OBJECTIVE
  To investigate the possible impact of thrombin on soluble Fms-like tyrosine kinase 1 (sFlt-1) expression in trophoblasts.
  
  
  METHODS
  Experimental.
  
  
  METHODS
  University hospital laboratory.
  
  
  METHODS
  A trophoblast cell line (HRT-8/SVneo) was treated with thrombin, protease-activated receptor 1 (PAR-1)-specific agonist SFLLERN, and thrombin antagonist PPACK.
  
  
  METHODS
  mRNA expression of sFlt-1, vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) in trophoblasts, with the use of real-time polymerase chain reaction; and the secretion of sFlt-1, VEGF, and PlGF protein from trophoblasts, with the use of ELISA.
  
  
  RESULTS
  Administration of thrombin (10 U/mL) and PAR-1-specific agonist SFLLRN (300 μmol/L) increased sFlt-1 mRNA expression (4.24 ± 0.74- and 4.21 ± 0.79-fold, respectively) and protein secretion (5.08 ± 0.42- and 1.89 ± 0.16-fold, respectively) in HRT-8/SVneo. The induction of sFlt-1 protein secretion by thrombin was dose dependent. The effect of thrombin was completely reduced by thrombin inhibitor PPACK. Thrombin increased mRNA expression of VEGF but did not change VEGF secretion and PlGF mRNA expression and secretion.
  
  
  CONCLUSIONS
  During placental development, thrombin, generated in the local hemorrhage of the uteroplacenta increases trophoblast expression of sFlt-1. Consequently, thrombin may contribute to the pathogenesis of preeclampsia.
authors: Obstetrics and Gynecology, University of Tokyo, Tokyo, Japan.
authors: Yin
authors: Y
authors: Zhao
authors: Kaori
authors: K
authors: Koga
authors: Yutaka
authors: Y
authors: Osuga
authors: Miwako
authors: M
authors: Nagai
authors: Gentaro
authors: G
authors: Izumi
authors: Masashi
authors: M
authors: Takamura
authors: Miyuki
authors: M
authors: Harada
authors: Yasushi
authors: Y
authors: Hirota
authors: Osamu
authors: O
authors: Yoshino
authors: Yuji
authors: Y
authors: Taketani
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D002460:Cell Line; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006490:Hemostatics / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000378:metabolism / Q000503:physiopathology*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics; D044463:Receptor, PAR-1 / Q000819:agonists / Q000378:metabolism; D018179:Receptors, Thrombin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism* / Q000494:pharmacology; D014327:Trophoblasts / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*; D010975:Platelet Aggregation Inhibitors
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D006490:Hemostatics; C000608036:PGF protein, human; D010446:Peptide Fragments; D011257:Pregnancy Proteins; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C082835:thrombin receptor peptide (42-47); D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D013917:Thrombin; C040308:phenylalanyl-prolyl-arginine-chloromethyl ketone; D010975:Platelet Aggregation Inhibitors