Fibronectinase activity in cultured human trophoblasts is mediated by urokinase-type plasminogen activator.

Abstract:

OBJECTIVE:Human trophoblast proteolytic activity is believed to have implications for early implantation events and maintenance of chorionic structural integrity later in gestation. Abnormal release of chorion-derived extracellular matrix proteins such as fibronectin may identify patients at risk for preterm labor and delivery. The aim of this study was to characterize the enzyme(s) potentially responsible for trophoblast-mediated proteolysis of fibronectin. STUDY DESIGN:Human term cytotrophoblasts were analyzed for their capacity to cleave fibronectin into discrete proteolytic fragments. Selective protease inhibitors were used to characterize trophoblast-derived enzymes with fibronectinase activity. Analysis and quantitation of fibronectin fragment release was determined by Western immunoblots and enzyme-linked immunosorbent assays. RESULTS:Fibronectinase activity in trophoblast cultures was found to be both cell mediated and secreted, with the release of discrete fibronectin fragments into the media. Cell-mediated proteolytic activity could be partially inhibited by serum, whereas conditioned media containing fibronectinase activity was completely inhibited by serum, a serine protease inhibitor, and a selective inhibitor of urokinase-type plasminogen activator. Digestion of fibronectin with pure urokinase produced a similar pattern of fibronectin fragments compared with fibronectinase-generated fragments. Immunodepletion of urokinase from trophoblast media abolished fibronectinase activity. CONCLUSIONS:Trophoblast-derived urokinase-type plasminogen activator has significant proteolytic activity in vitro with the capability of cleaving fibronectin into discrete fragments. In early pregnancy this activity could be part of the enzymatic cascade leading to uterine extracellular matrix remodeling and implantation. Later in pregnancy trophoblast derived urokinase could promote normal or inflammation-induced changes in the chorionic extracellular matrix.

journal_name

Am J Obstet Gynecol

authors

Monzón-Bordonaba F,Wang CL,Feinberg RF

doi

10.1016/s0002-9378(97)80012-9

subject

Has Abstract

pub_date

1997-01-01 00:00:00

pages

58-65

issue

1 Pt 1

eissn

0002-9378

issn

1097-6868

pii

S0002937897706501

journal_volume

176

pub_type

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