ArticleThe American journal of pathology2019
Role of Endoplasmic Reticulum Stress in Proinflammatory Cytokine-Mediated Inhibition of Trophoblast Invasion in Placenta-Related Complications of Pregnancy.
Article in The American journal of pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 58 citations in OpenAlex.
- Investigation of Endoplasmic Reticulum Stress in Pregnant Women with Hyperemesis Gravidarum.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Investigation of Endoplasmic Reticulum Stress in Pregnant Women with Hyperemesis Gravidarum.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Article
- IGFBP3 repression driven by inflammation links air pollution to placental and developmental defects.EMBO molecular medicine · 2026Article
- Review
- Fluid percussion trauma to the placental trophoblast triggers multifaceted injury mechanisms, including mitochondrial stress response, immune dysregulation, cytoskeletal, endothelial, and angiogenic signaling cascades.Frontiers in cell and developmental biology · 2026Article
- Maternal causation of early-onset pre-eclampsia: excessive endometrial gland-derived apolipoprotein D induces placental ferroptosis and developmental abnormalities.Journal of biomedical science · 2025Article
- Navigating Cellular Stress: Endoplasmic Reticulum Stress and the Unfolded Protein Response in the Molecular Pathogenesis of Preeclampsia.Cell biochemistry and biophysics · 2025Review
- Serum estradiol (E2), progesterone (P), and human chorionic gonadotropin (HCG), D-dimer (D-D) fibrinogen (FIB) levels after low molecular weight heparin sodium on preventing miscarriage in patients with adverse pregnancy and delivery.Journal of medical biochemistry · 2025Article
- AβJournal of molecular histology · 2024Article
- Article
- A stress paradox: the dual role of the unfolded protein response in the placenta.Frontiers in endocrinology · 2024Review
- Article
- Mechanism of histone deacetylase HDAC2 in FOXO3-mediated trophoblast pyroptosis in preeclampsia.Functional & integrative genomics · 2023Article
- The Role of Interferon (IFN)-γ in Extravillous Trophoblast Cell (EVT) Invasion and Preeclampsia Progression.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- Article
- Origination of LTR Retroelement-Derived NYNRIN Coincides with Therian Placental Emergence.Molecular biology and evolution · 2022Article
- The Targeting of Nuclear Factor Kappa B by Drugs Adopted for the Prevention and Treatment of Preeclampsia.International journal of molecular sciences · 2022Review
- Endoplasmic Reticulum Stress and the Unfolded Protein Response in Cerebral Ischemia/Reperfusion Injury.Frontiers in cellular neuroscience · 2022Review
- Unfolded protein response triggers differential apoptotic mechanisms in ovaries and early embryos exposed to maternal type 1 diabetes.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 4 countries.
Funding
Abstract
Shallow extravillous trophoblast (EVT) invasion is central to the pathophysiology of many pregnancy complications. Invasion is mediated partially by matrix metalloproteinases (MMPs). MMP-2 is highly expressed in early pregnancy. MMP activity can be regulated by proinflammatory cytokines, which also induce endoplasmic reticulum (ER) stress in other cells. We investigated whether proinflammatory cytokines regulate MMP-2 activity through ER stress response pathways in trophoblast before exploring potential regulatory mechanisms. There was increased immunoreactivity of heat shock 70-kDa protein 5, also known as 78-kDa glucose regulated protein, in cells of the placental bed, including EVTs, in cases of early-onset preeclampsia compared with normotensive controls. Treating EVT-like JEG-3 and HTR8/SVneo cells with ER stress inducers (tunicamycin and thapsigargin) suppressed MMP2 mRNA and protein expression, secretion, and activity and reduced their invasiveness. A cocktail of proinflammatory cytokines (IL-1β, tumor necrosis factor-α, and interferon-γ) suppressed MMP-2 activity in JEG-3 cells and was accompanied by activation of the PKR-like ER kinase (PERK)-eukaryotic translation initiation factor 2A (EIF2A) arm of the ER stress pathway. Knockdown of ATF4, a downstream transcriptional factor of the PERK-EIF2A pathway, by small interference RNA, restored MMP2 expression but not cellular proteins. However, suppression of EIF2A phosphorylation with a PERK inhibitor, GSK2606414, under ER stress, restored MMP-2 protein. ER stress regulates MMP-2 expression at both the transcriptional and translational levels. This study provides the first mechanistic linkage by which proinflammatory cytokines may modulate trophoblast invasion through ER stress pathways.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.