title: Prostasin and matriptase (ST14) in placenta from preeclamptic and healthy pregnant women.
abstract: OBJECTIVE
  Preeclampsia is characterized by disturbed placentation, hypertension, proteinuria, and suppression of plasma renin, angiotensin II, and aldosterone. Regulated activity of tissue serine proteases, prostasin, and matriptase is necessary for normal placental development in mice. Prostasin activates the renal epithelial sodium channel. We hypothesized that preeclampsia is associated with low prostasin expression in placenta and spillover of prostasin into urine across the defect glomerular barrier.
  
  
  METHODS
  In a cross-sectional study, 20 healthy pregnant women and 20 patients suspected of preeclampsia were included. Plasma and urine was obtained before delivery, and placental biopsies were taken immediately after delivery (mean gestational age: control 39 and preeclampsia 38 weeks).
  
  
  RESULTS
  Patients with preeclampsia displayed lower levels of aldosterone in plasma and in spot urine normalized for creatinine (P = 0.0001). Prostasin, matriptase, hepatocyte growth factor activator inhibitor type 1 (HAI-1) and 2, and nexin-1 mRNA abundances were not different in placental tissue between groups. Prostasin mRNA in placenta correlated directly with nexin-1 and HAI-1 mRNA, but not with matriptase mRNA. Plasma prostasin and placental homogenate prostasin and nexin-1 protein levels did not differ between groups. Activated, arginine 614 (Arg614)-cleaved matriptase was not detectable in placentas. Western blotting showed significant elevated levels of prostasin in urine from preeclamptic patients that correlated with urine albumin. Placenta and plasma prostasin did not correlate to aldosterone or placental weight.
  
  
  CONCLUSIONS
  Preeclampsia is not associated with altered prostasin in placenta or plasma at term, but with increased prostasin in urine. An impact of prostasin-matriptase on placental development is likely to be at the level of activity and not protein abundance.
authors: aThe Research Unit, Department of Obstetrics and Gynaecology, Odense University HospitalbDepartment of Cardiovascular and Renal Research, Institute for Molecular Medicine, University of Southern DenmarkcDepartment for Cellular and Molecular Medicine, University of Copenhagen, CopenhagendHCA Research, Hans Christian Andersen Children's HospitaleInstitute for Clinical Research, University of Southern Denmark, Odense, Denmark.
authors: Britta
authors: B
authors: Frederiksen-Møller
authors: Jan S
authors: JS
authors: Jørgensen
authors: Mie R
authors: MR
authors: Hansen
authors: Oliver
authors: O
authors: Krigslund
authors: Lotte K
authors: LK
authors: Vogel
authors: Louise B
authors: LB
authors: Andersen
authors: Boye L
authors: BL
authors: Jensen
mesh_terms: D000328:Adult; D000450:Aldosterone / Q000097:blood / Q000652:urine; D000818:Animals; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D053503:Epithelial Sodium Channels; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D009929:Organ Size; D010920:Placenta / Q000378:metabolism* / Q000473:pathology*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D053491:Proteinase Inhibitory Proteins, Secretory / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D058258:Serpin E2 / Q000235:genetics / Q000378:metabolism; D000099271:Prostasin
chemical_list: D000450:Aldosterone; D053503:Epithelial Sodium Channels; D008562:Membrane Glycoproteins; D053491:Proteinase Inhibitory Proteins, Secretory; D012333:RNA, Messenger; D012697:Serine Endopeptidases; D058258:Serpin E2; D000099271:Prostasin; C109149:SPINT1 protein, human; C109148:SPINT2 protein, human; C485595:matriptase