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Cited by 95Preterm Birth and ChorioamnionitisProtease and Inhibitor MechanismsBlood Coagulation and Thrombosis Mechanisms

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

Mackenzie, Andrew P., Schatz, Frederick, Krikun, Graciela, Funai, Edmund F., Kadner, Susan, Lockwood, Charles J.·2004·American Journal of Obstetrics and Gynecology
DOI 10.1016/j.ajog.2004.08.003
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Abstract

Objective 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.Study design 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.Results 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.Conclusion 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.

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  • Decidual bleeding leads to release of excess thrombin, which is generated by tissue factor expressed on decidual cells to promote hemostasis.

    “Decidual bleeding leads to release of excess thrombin, which is generated by tissue factor expressed on decidual cells to promote hemostasis (17, 18).”

    From Placental abruption at near-term and term gestations: Pathophysiology, epidemiology, diagnosis, and management (2023) · cites this paper as [17]

  • Thrombin results in degradation of extracellular matrix and further endothelial injury from enhanced expression of matrix metalloproteinases and release of pro-inflammatory cytokines such as interleukin-8.

    “This results in degradation of extracellular matrix and further endothelial injury from enhanced expression of matrix metalloproteinases (17) as well as the release of pro-inflammatory cytokines, such as interleukin-8 (19).”

    From Placental abruption at near-term and term gestations: Pathophysiology, epidemiology, diagnosis, and management (2023) · cites this paper as [17]

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Authors
Mackenzie, A. P., Schatz, F., Krikun, G., Funai, E. F., Kadner, S., & Lockwood, C. J.
Affiliations
  • New York University (US)
  • Yale University (US)
Corresponding author
Lockwood, Charles J.
ORCID
Venue
American Journal of Obstetrics and Gynecology
Publisher
Elsevier BV
Published
2004-12
Volume
191
Issue
6
Pages
1996-2001
ISSN
0002-9378 (ISSN-L)
DOI
10.1016/j.ajog.2004.08.003
OpenAlex
W2027078534
Cited by
95
References
34
Citations by year
2026: 2 · 2025: 4 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 6 · 2017: 5 · 2016: 5 · 2015: 4 · 2014: 8 · 2013: 5 · 2012: 5
FWCI
3.59
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • American Journal of Obstetrics and Gynecology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords
placental abruption, thrombin, matrix metalloproteinase-3, stromelysin-1, decidual cells, progesterone, estradiol, extracellular matrix degradation, preterm birth
MeSH terms
Base Sequence, Cells, Cultured, Decidua, Female, Extraembryonic Membranes, Premature Rupture of Fetal Membranes, Humans, Molecular Sequence Data, Pregnancy, Progestins, Reference Values, RNA, Messenger, Sensitivity and Specificity, Thrombin, Blotting, Northern, Matrix Metalloproteinase 3, Reverse Transcriptase Polymerase Chain Reaction, In Vitro Techniques

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