ArticleThe Journal of clinical endocrinology and metabolism2014
Prostaglandin E2 regulates its own inactivating enzyme, 15-PGDH, by EP2 receptor-mediated cervical cell-specific mechanisms.
Article in The Journal of clinical endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Up-regulation of cytosolic prostaglandin E synthase in fetal-membrane and amniotic prostaglandin E2 accumulation in labor.PloS one · 2021Article
- 15-Keto-PGEThe Journal of biological chemistry · 2020Article
- Thrombin Alters Human Endometrial Stromal Cell Differentiation During Decidualization.Reproductive sciences (Thousand Oaks, Calif.) · 2019Article
- Peripherally Restricted, Highly Potent, Selective, Aqueous-Soluble EP2 Antagonist with Anti-Inflammatory Properties.Molecular pharmaceutics · 2018Article
- Endometrial stromal cell attachment and matrix homeostasis in abdominal wall endometriomas.Human reproduction (Oxford, England) · 2018Observational
- Prostaglandin dehydrogenase is a target for successful induction of cervical ripening.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Increased Expression of 15-Hydroxyprostaglandin Dehydrogenase in Spinal Astrocytes During Disease Progression in a Model of Amyotrophic Lateral Sclerosis.Cellular and molecular neurobiology · 2017Article
- Nrf2 Activation Inhibits Effects of Thrombin in Human Amnion Cells and Thrombin-Induced Preterm Birth in Mice.The Journal of clinical endocrinology and metabolism · 2016Article
- An elevated amniotic fluid prostaglandin F2α concentration is associated with intra-amniotic inflammation/infection, and clinical and histologic chorioamnionitis, as well as impending preterm delivery in patients with preterm labor and intact membranes.The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2016Article
- Umbilical cord prostaglandins in term and preterm parturition.The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2016Article
- Macrophage gene expression associated with remodeling of the prepartum rat cervix: microarray and pathway analyses.PloS one · 2015Article
- Inhibitory effect of insulin-like growth factor-binding protein-7 (IGFBP7) on in vitro angiogenesis of vascular endothelial cells in the rat corpus luteum.The Journal of reproduction and development · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
contextProstaglandins play important roles in parturition and have been used to induce cervical ripening and labor. Prior to cervical ripening at term, 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is highly expressed in the cervix and metabolizes cyclooxygenase-2-mediated increases in active prostaglandin E2 (PGE2) to inactive 15-keto PGE2. At term, 15-PGDH gene expression decreases and PGE2 accumulates, leading to cervical ripening and labor. Previously, we found that the cervical isoform of microphthalmia-associated transcription factor (MiTF-CX) serves as a progestational transcription factor that represses IL-8 and hypoxia-mediated increases in cyclooxygenase-2.
objectiveWe tested the hypothesis that PGE2 regulates its own inactivation through MiTF-CX.
designWe used human cervical stromal cells to investigate the regulation of 15-PGDH.
settingThis was a laboratory-based study using cells from clinical tissue samples.
main outcome measuresWe evaluated the mechanisms by which PGE2 regulates 15-PGDH in human cervical stromal cells.
resultsPGE2 repressed MiTF-CX and 15-PGDH, whereas ectopic overexpression of MiTF-CX induced 15-PGDH expression levels. Stabilization of HIF-1α by deferoxamine resulted in concomitant down-regulation of MiTF-CX and 15-PGDH. Ectopic overexpression of MiTF-CX abrogated PGE2- and deferoxamine-mediated loss of MiTF-CX and 15-PGDH. PGE2-induced loss of MiTF-CX and 15-PGDH was mediated through prostaglandin E2 receptor (EP2) receptors (PTGER2), but not cAMP.
conclusionsThe 15-PGDH gene is a MiTF-CX target gene in cervical stromal cells and is down-regulated by PGE2 through EP2 receptors. The findings suggest that EP2 receptor-specific antagonists may be used as an adjunct to present clinical management for the prevention of preterm cervical ripening and preterm labor.
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