ArticleJournal of leukocyte biology2016
Role of Notch signaling during lipopolysaccharide-induced preterm labor.
Article in Journal of leukocyte biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Lipopolysaccharide-mediated macrophage polarization, conserved pathogenesis, and implications for peripheral neuropathy: a systematic review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Pooled it
- Inflammation at the maternal-fetal interface: a perspective on interacting risk factors for preterm birth in sub-Saharan African women living with HIV.Frontiers in immunology · 2026Review
- The landscape of decidual immune cells at the maternal-fetal interface in parturition and preterm birth.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Macrophages: a double-edged sword in female reproduction and disorders.Experimental & molecular medicine · 2025Review
- Barrier genes are associated with preterm birth.Frontiers in medicine · 2025Article
- Review
- Altered expression of Notch signaling, Tlr receptors, and surfactant protein expression after prostaglandin inhibition may be associated with the delayed labor in LPS-induced mice.Journal of assisted reproduction and genetics · 2022Article
- Review
- Relationship of Notch Signal, Surfactant Protein A, and Indomethacin in Cervix During Preterm Birth: Mast Cell and Jagged-2 May Be Key in Understanding Infection-mediated Preterm Birth.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2022Article
- Article
- Immunobiology of Acute Chorioamnionitis.Frontiers in immunology · 2020Review
- Misoprostol-Induced Modification of the Notch Signaling Pathway in the Human Cervix.Reproductive sciences (Thousand Oaks, Calif.) · 2019Article
- Macrophage Polarization in Physiological and Pathological Pregnancy.Frontiers in immunology · 2019Review
- CD71+ erythroid cells from neonates born to women with preterm labor regulate cytokine and cellular responses.Journal of leukocyte biology · 2018Article
- The curious case of vacuolar ATPase: regulation of signaling pathways.Molecular cancer · 2018Review
- Modulators of the Balance between M1 and M2 Macrophages during Pregnancy.Frontiers in immunology · 2017Review
- Contributions to the dynamics of cervix remodeling prior to term and preterm birth.Biology of reproduction · 2017Review
- Toll-like 4 receptor /NFκB inflammatory/miR-146a pathway contributes to the ART-correlated preterm birth outcome.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Notch signaling pathways exert effects throughout pregnancy and are activated in response to TLR ligands. To investigate the role of Notch signaling in preterm labor, Notch receptors (Notch1-4), its ligand Delta-like protein-1, transcriptional repressor hairy and enhancer of split-1, and Notch deregulator Numb were assessed. Preterm labor was initiated on gestation d 14.5 by 1 of 2 methods: 1) inflammation-induced preterm labor: intrauterine injection of LPS (a TLR4 agonist) and 2) hormonally induced preterm labor: subcutaneous injection of mifepristone. Delta-like protein-1, Notch1, and hairy and enhancer of split-1 were elevated significantly, and Numb was decreased in the uterus and placenta of inflammation-induced preterm labor mice but remained unchanged in hormonally induced preterm labor compared with their respective controls. F4/80(+) macrophage polarization was skewed in the uterus of inflammation-induced preterm labor toward M1-positive (CD11c(+)) and double-positive [CD11c(+) (M1) and CD206(+) (M2)] cells. This process is dependent on activation of Notch signaling, as shown by suppression of M1 and M2 macrophage-associated cytokines in decidual macrophages in response to γ-secretase inhibitor (an inhibitor of Notch receptor processing) treatment ex vivo. γ-Secretase inhibitor treatment also diminished the LPS-induced secretion of proinflammatory cytokines and chemokines in decidual and placental cells cultured ex vivo. Furthermore, treatment with recombinant Delta-like protein-1 ligand enhanced the LPS-induced proinflammatory response. Notch ligands (Jagged 1 and 2 and Delta-like protein-4) and vascular endothelial growth factor and its receptor involved in angiogenesis were reduced significantly in the uterus and placenta during inflammation-induced preterm labor. These results suggest that up-regulation of Notch-related inflammation and down-regulation of angiogenesis factors may be associated with inflammation-induced preterm labor but not with hormonally induced preterm labor.
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Registered trials
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