ArticlePlacenta2007
Role of hypoxia-inducible transcription factors 1alpha and 2alpha in the regulation of plasminogen activator inhibitor-1 expression in a human trophoblast cell line.
Article in Placenta, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
20 citing papers in PubMed, 34 citations in OpenAlex.
- A novel multiplex RNAi therapy simultaneously targets Hif1a and Hif2a to defy retinal degeneration in two models of AMD.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- The HIF axes in cancer: angiogenesis, metabolism, and immune-modulation.Trends in biochemical sciences · 2025Review
- In vitro differentiation of macaque extravillous trophoblasts in a low oxygen environment.Placenta · 2025Article
- The Role of Catestatin in Preeclampsia.International journal of molecular sciences · 2024Review
- Oncostatin M, Serpins, and Oxidative Stress in Extracellular Matrix Remodeling and Arteriovenous Fistula Maturation.Cardiology and cardiovascular medicine · 2023Article
- Changes of new coagulation markers in healthy pregnant women and establishment of reference intervals in Changsha.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022Article
- Downregulation of HIF-2α Enhances Apoptosis and Limits Invasion in Human Placental JEG-3 Trophoblast Cells.Reproductive sciences (Thousand Oaks, Calif.) · 2021Article
- HGF regulate HTR-8/SVneo trophoblastic cells migration/invasion under hypoxic conditions through increased HIF-1α expression via MAPK and PI3K pathways.Journal of cell communication and signaling · 2019Article
- Epsilon-aminocaproic acid prevents high glucose and insulin induced-invasiveness in MDA-MB-231 breast cancer cells, modulating the plasminogen activator system.Molecular and cellular biochemistry · 2018Article
- Role of Plasminogen Activator Inhibitor Type 1 in Pathologies of Female Reproductive Diseases.International journal of molecular sciences · 2017Review
- High glucose and insulin enhance uPA expression, ROS formation and invasiveness in breast cancer-derived cells.Cellular oncology (Dordrecht, Netherlands) · 2016Article
- Knockdown of hypoxia inducible factor-2α inhibits cell invasion via the downregulation of MMP-2 expression in breast cancer cells.Oncology letters · 2016Article
- Phospholipid scramblase 1 (PLSCR1) in villous trophoblast of the human placenta.Histochemistry and cell biology · 2015Article
- Human adaptation to the hypoxia of high altitude: the Tibetan paradigm from the pregenomic to the postgenomic era.Journal of applied physiology (Bethesda, Md. : 1985) · 2014Review
- Bioinformatic analysis of benzo-α-pyrene-induced damage to the human placental insulin-like growth factor-1 gene.Reproductive sciences (Thousand Oaks, Calif.) · 2013Article
- Gene targeting in primary human trophoblasts.Placenta · 2012Review
- Natural selection on EPAS1 (HIF2alpha) associated with low hemoglobin concentration in Tibetan highlanders.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Article
- Placental expression of ceruloplasmin in pregnancies complicated by severe preeclampsia.Laboratory investigation; a journal of technical methods and pathology · 2008Article
- Beyond oxygen: complex regulation and activity of hypoxia inducible factors in pregnancy.Human reproduction updateReview
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The plasminogen activator inhibitors (PAIs) play critical roles in regulating hemostatic and invasive functions of trophoblasts through suppression of plasmin-dependent fibrinolysis and extracellular matrix degradation. The expression of PAI-1 is increased under hypoxic conditions, although the mechanism remains incompletely understood. In the current study we used HTR-8/SVneo cells, a first trimester extravillous trophoblast cell line, and siRNA technology to examine the role of hypoxia-inducible transcription factors (HIFs)-1alpha and -2alpha in the regulation of PAI-1 expression. Using serum-containing and serum-free media culture media it was initially noted that levels of PAI-1, but not PAI-2 protein, were markedly induced by hypoxic (2-3% oxygen) treatment. Under hypoxic conditions, Western blotting revealed that the presence of siRNAs to HIF-1alpha and HIF-2alpha suppressed expression of their respective proteins, whereas treatment with non-targeting and cyclophilin B siRNAs did not. Importantly, incubation with siRNA to HIF-1alpha or HIF-2alpha alone reduced PAI-1 protein levels to a similar extent, with the combined treatment inducing a more profound effect. The presence of HIF siRNAs reduced levels of PAI-1 mRNA as measured by quantitative real-time PCR, indicating that HIF-1alpha and HIF-2 alpha regulate PAI-1 expression at a transcriptional level. These results indicate that both HIF-1alpha and HIF-2alpha play important and similar roles in hypoxia-mediated stimulation of PAI-1 expression in HTR-8/SVneo cells. Our findings provide insight into the physiological regulation of trophoblast PAI-1 expression in early pregnancy when placental oxygen levels are low, as well as a mechanism for over-expression of placental PAI-1 noted in pregnancies with preeclampsia.
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Registered trials
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.