ArticleBiology of reproduction2019
Oxidative stress-induced downregulation of glycogen synthase kinase 3 beta in fetal membranes promotes cellular senescence†.
Article in Biology of reproduction, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Alcohol-Associated Hepatocarcinogenesis: Wnt/β-Catenin in Action.The American journal of pathology · 2026Pooled it
- Contribution of p38 MAPK in liver fibrosis: An overview of mechanisms, signaling pathways, and therapeutic targets (Review).International journal of molecular medicine · 2026Review
- Protective Effects of Eugenia uniflora Red Fruit on Brain in a Rat Model of Type 2 Diabetes: Mechanistic Insights.Neurochemical research · 2025Article
- Article
- Decidual Cells Induce Release of Free and Exosome-Bound Interferon Epsilon From Vaginal Epithelial Cells.American journal of reproductive immunology (New York, N.Y. : 1989) · 2025Article
- The Impacts of TNF-α-Induced Inflammation on Amnion Epithelial Cells: Exploring Stem Cell Gene Expression, Senescence, Inflammatory Responses, and Cellular Transition.American journal of reproductive immunology (New York, N.Y. : 1989) · 2025Article
- Nuclear Translocation of S100A9 Triggers Senescence of Human Amnion Fibroblasts by De-Repressing LINE1 Via Heterochromatin Erosion at Parturition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The role of amniotic epithelial cells in preterm birth: mechanisms and clinical implications.Frontiers in cell and developmental biology · 2025Review
- Long-term outcome of childhood and adolescent patients with craniopharyngiomas: a single center retrospective experience.BMC cancer · 2024Article
- Naringin Prevents Diabetic-Induced Dysmetabolism in Male Wistar Rats by Modulating GSK-3 Activities and Oxidative Stress-Dependent Pathways.Cell biochemistry and biophysics · 2024Article
- Histologic Evidence of Epithelial-Mesenchymal Transition and Autophagy in Human Fetal Membranes.The American journal of pathology · 2024Article
- Frontiers in the Etiology and Treatment of Preterm Premature Rupture of Membrane: From Molecular Mechanisms to Innovative Therapeutic Strategies.Reproductive sciences (Thousand Oaks, Calif.) · 2024Review
- Spatial transcriptomics of fetal membrane-Decidual interface reveals unique contributions by cell types in term and preterm births.PloS one · 2024Article
- Decreased level of TREM like Transcript 1 (TLT-1) is associated with prematurity and promotes the in-utero inflammatory response to maternal lipopolysaccharide (LPS) exposure.American journal of reproductive immunology (New York, N.Y. : 1989) · 2023Article
- Review on new approach methods to gain insight into the feto-maternal interface physiology.Frontiers in medicine · 2023Review
- Silencing P38 MAPK reduces cellular senescence in human fetal chorion trophoblast cells.American journal of reproductive immunology (New York, N.Y. : 1989) · 2023Article
- Adapting an organ-on-chip device to study the effect of fetal sex and maternal race/ethnicity on preterm birth related intraamniotic inflammation leading to fetal neuroinflammation.American journal of reproductive immunology (New York, N.Y. : 1989) · 2022Article
- Stress signaler p38 mitogen-activated kinase activation: a cause for concern?Clinical science (London, England : 1979) · 2022Article
- Irregular Expression of Cellular Stress Response Markers in the Placenta of Women with Chronic Venous Disease.Antioxidants (Basel, Switzerland) · 2022Article
- Impact of Oxidative Stress on Molecular Mechanisms of Cervical Ripening in Pregnant Women.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveOxidative stress (OS)-induced stress signaler p38 mitogen-activated protein kinase (p38MAPK) activation and fetal membrane senescence are associated with parturition. This study determined changes in glycogen synthase kinase 3 beta (GSK3β) and its regulation by p38MAPK in effecting senescence to further delineate the molecular mechanism involved in senescence.
methodsPrimary human amnion epithelial cells and amnion mesenchymal cells were treated with cigarette smoke extract (CSE, OS inducer). Expression of total and phosphorylated GSK3β and p38MAPK, and that of GSK3β's downstream targets: beta-catenin (β-Cat) and nuclear factor erythroid 2-related factor 2 (Nrf2) (western blot analysis), cell cycle regulation and senescence (flow cytometry) were determined. The specificity of GSK3β and p38MAPK's mechanistic role was tested by co-treating cells with their respective inhibitors, CHIR99021 and SB203580. Exosomal secretion of β-Cat from OS-induced cells was confirmed by immunofluorescence confocal microscopy and western blot.
resultsOS induced by CSE resulted in phosphorylation of GSK3β (inactivation) and p38MAPK (activation) that was associated with cell cycle arrest and senescence. Inhibitors to GSK3β and p38MAPK verified their roles. Glycogen synthase kinase 3 beta inactivation was associated with nuclear translocation of antioxidant Nrf2 and exosomal secretion of β-Cat.
conclusionsOS-induced P-p38MAPK activation is associated with functional downregulation of GSK3β and arrest of cell cycle progression and senescence of amnion cells. Lack of nuclear translocation of β-Cat and its excretion via exosomes further supports the postulation that GSK3β down-regulation by p38MAPK may stop cell proliferation preceding cell senescence. A better understanding of molecular mechanisms of senescence will help develop therapeutic strategies to prevent preterm birth.
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Registered trials
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