Reduction of extracellular matrix protein expression in human amnion epithelial cells by glucocorticoids: a potential role in preterm rupture of the fetal membranes.
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.
Guller
S
S
Department of Obstetrics/Gynecology, Mount Sinai Medical Center, New York, New York 10029, USA.
Kong
L
L
Wozniak
R
R
Lockwood
C J
CJ
D000328:Adult; D000650:Amnion / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D002585:Cesarean Section; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000503:physiopathology*; D005353:Fibronectins / Q000032:analysis / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007700:Kinetics; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D013997:Time Factors
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D012333:RNA, Messenger; D003907:Dexamethasone; D006854:Hydrocortisone