Reduction of extracellular matrix protein expression in human amnion epithelial cells by glucocorticoids: a potential role in preterm rupture of the fetal membranes
S Guller, L Kong, R Wozniak and CJ Lockwood
Department of Obstetrics/Gynecology, Mount Sinai Medical Center, New York, New York 10029, USA.
Low levels of expression of extracellular matrix (ECM) proteins in
chorioamniotic membranes is a characteristic of prematurely ruptured
membranes, a condition associated with 40% of preterm deliveries. In light
of the rise in levels of glucocorticoids (GC) in amniotic fluid associated
with preterm labor, in the present study we examined the effects of GC on
the expression of major ECM proteins in cultures of amnion epithelial cells
recovered after digestion of human term amnions. Amnion cells were
maintained with and without 10(-7) mol/L dexamethasone (DEX), and levels of
the ECM protein fibronectin (FN) were determined by enzyme-linked
immunosorbent assay. DEX treatment reduced FN expression in amnion
epithelial cells to 15-30% of control levels and reduced FN expression in
placental cells to 30-50% of control levels. Conversely, DEX treatment
weakly stimulated FN expression in chorion cell cultures. DEX treatment did
not affect the total level of amnion cell protein, indicating that the
effects of DEX in amnion cells did not result from a general reduction in
protein synthesis. Cortisol and DEX reduced FN expression in amnion cells,
with half-maximal effective concentrations of approximately 60 and 8
nmol/L, respectively. In immunoprecipitation studies, DEX treatment reduced
FN and collagen III synthesis to 20% of control levels, suggesting that GC
may coordinately reduce the synthesis of major ECM proteins in amnion
cells. Similarly, DEX treatment reduced the levels of FN messenger
ribonucleic acids in amnion cells to approximately 15% of control levels.
DEX treatment also promoted a marked reduction in FN expression in amnion
cells cultured in serum-free medium to 10-50% of control levels. Our
results indicate that GC negatively regulate ECM protein expression in
amnion epithelial cells, suggesting a potential role in the genesis of
altered fetal membrane ECM protein expression associated with prematurely
ruptured membranes.
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