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.

CONCLUSION:

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: Britta Frederiksen-Møller, Jan S Jørgensen, Mie R Hansen, Oliver Krigslund, Lotte K Vogel, Louise B Andersen, Boye L Jensen
• Journal: Journal of hypertension (J Hypertens) Vol. 34 Issue 2 Pg. 298-306 (Feb 2016) ISSN: 1473-5598 [Electronic] England
• PMID: 26867056 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Epithelial Sodium Channels
• Membrane Glycoproteins
• Proteinase Inhibitory Proteins, Secretory
• RNA, Messenger
• SPINT1 protein, human
• SPINT2 protein, human
• Serpin E2
• Aldosterone
• Serine Endopeptidases
• matriptase
• prostasin

Topics

• Adult
• Aldosterone (blood, urine)
• Animals
• Case-Control Studies
• Cross-Sectional Studies
• Epithelial Sodium Channels
• Female
• Humans
• Membrane Glycoproteins (genetics)
• Organ Size
• Placenta (metabolism, pathology)
• Pre-Eclampsia (metabolism)
• Pregnancy
• Proteinase Inhibitory Proteins, Secretory (genetics)
• RNA, Messenger (metabolism)
• Serine Endopeptidases (genetics, metabolism)
• Serpin E2 (genetics, metabolism)