Mechanisms of abruption-induced premature rupture of the fetal membranes: Thrombin enhanced decidual matrix metalloproteinase-3 (stromelysin-1) expression

Autor: Frederick Schatz, Graciela Krikun, Charles J. Lockwood, Andrew P. Mackenzie, Edmund F. Funai, Susan Kadner
Rok vydání: 2004
Předmět:
Zdroj: American Journal of Obstetrics and Gynecology. 191:1996-2001
ISSN: 0002-9378
DOI: 10.1016/j.ajog.2004.08.003
Popis: The aim of the study was to evaluate thrombin and progestin effects on matrix metalloproteinase-3 expression in term decidual cells as a mechanism of abruption-related preterm delivery.Decidual cells were isolated by standard techniques, purified to homogeneity, grown to confluence, and passaged. Cultures were primed with 10 (-8) M estradiol or estradiol plus 10 (-7) progestin and then incubated in a defined medium with corresponding steroid(s) plus or minus thrombin or the protease-activated thrombin receptor-1 agonist for 24 hours. Secreted matrix metalloproteinase-3 levels were assessed by enzyme-linked immunosorbent assay, and immunoblotting and messenger RNA levels were measured by Northern blotting and quantitative reverse transcription-polymerase chain reaction.Immunoreactive matrix metalloproteinase-3 levels were inhibited 66% by estradiol plus progestin versus estradiol ( P.05). Thrombin elicited a dose-dependent reversal in this progestin inhibition, producing a 2.5-fold increase at 2.5 U/mL ( P.05) that attained 33% of matrix metalloproteinase-3 levels in parallel incubations with estradiol plus thrombin. Protease-activated thrombin receptor-1 agonist mimicked 60% of thrombin-enhanced matrix metalloproteinase-3 output. Immunoblotting validated the enzyme-linked immunosorbent assay results. Northern blotting and quantitative reverse transcription-polymerase chain reaction demonstrated corresponding effects on steady-state messenger RNA levels.Abruption-generated thrombin promotes preterm delivery by mediating fetal membrane extracellular matrix degradation via enhanced decidual cell matrix metalloproteinase-3 expression, whereas progesterone blunts this thrombin-induced effect.
Databáze: OpenAIRE