ArticleScientific reports2018
HIF-2α, but not HIF-1α, mediates hypoxia-induced up-regulation of Flt-1 gene expression in placental trophoblasts.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 59 citations in OpenAlex.
- Pregnancy-related disorders: molecular mechanisms and management.Molecular biomedicine · 2026Review
- Understanding physiological adaptations of pregnancy to the chronic hypoxia of high altitude to inform obstetrical and neonatal care.Physiological reviews · 2026Review
- Regulation of PDGF-BB signaling in placental pericytes by soluble PDGFRβ isoforms: implications for fetoplacental vascular development.Angiogenesis · 2026Article
- HIF-1α mediated placental ischemic signaling in the development of early-onset preeclampsia.Redox biology · 2026Review
- Preeclampsia Is a Double-Hit Vascular Disorder: The VEGF-HO-1-CSE Axis.Biomolecules · 2026Review
- Trophoblast adaptation to hypoxia: balance and dysfunction.Cell communication and signaling : CCS · 2025Review
- The molecular pathogenesis of placenta accreta spectrum disorder and its clinical applications.Archives of gynecology and obstetrics · 2025Review
- The Etiopathogenesis of Preeclampsia: Where Do We Stand Now?Journal of clinical medicine · 2025Review
- The uteroplacental circulation at high altitude: adaptation and maladaptation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Article
- Review
- Research trajectory of the mechanism of preeclampsia: a scientometric perspective.Journal of health, population, and nutrition · 2025Article
- GPER Stimulation Attenuates Cardiac Dysfunction in a Rat Model of Preeclampsia.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Synergistic rheumatoid arthritis therapy by interrupting the detrimental feedback loop to orchestrate hypoxia M1 macrophage polarization using an enzyme-catalyzed nanoplatform.Bioactive materials · 2024Article
- Metabolic reprogramming of hypoxic tumor-associated macrophages through CSF-1R targeting favors treatment efficiency in colorectal cancers.Journal for immunotherapy of cancer · 2024Article
- Biological hypoxia in pre-transplant human pancreatic islets induces transplant failure in diabetic mice.Scientific reports · 2024Article
- Extravillous trophoblast cell lineage development is associated with active remodeling of the chromatin landscape.Nature communications · 2023Article
- The Complex Relationship between Hypoxia Signaling, Mitochondrial Dysfunction and Inflammation in Calcific Aortic Valve Disease: Insights from the Molecular Mechanisms to Therapeutic Approaches.International journal of molecular sciences · 2023Review
- Connecting G protein-coupled estrogen receptor biomolecular mechanisms with the pathophysiology of preeclampsia: a review.Reproductive biology and endocrinology : RB&E · 2023Review
- Hypoxia induces downregulation of the tumor-suppressive sST2 in colorectal cancer cells via the HIF-nuclear IL-33-GATA3 pathway.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Placental hypoxia and elevated levels of circulating soluble Fms-like tyrosine kinase-1 (sFlt-1), an anti-angiogenic factor, are closely related to the pathogenesis of preeclampsia. Although sFlt-1 secretion from the placental trophoblasts is increased under hypoxic conditions, the underlying molecular mechanism remains unclear. Previously, an authentic hypoxia response element in the Flt-1 gene promoter was shown to be a potential binding site for hypoxia-inducible factors (HIFs). Here, we investigated the roles of HIF-1α and HIF-2α in Flt-1 gene expression in trophoblast-derived choriocarcinoma cell lines and cytotrophoblasts exposed to hypoxic conditions. In the cell lines, increased expression of sFlt-1 splice variants and nuclear accumulation of HIF-1α and HIF-2α were observed after hypoxic stimulation. A specific small interfering RNA or an inhibitor molecule targeting HIF-2α decreased hypoxia-induced up-regulation of Flt-1 gene expression. Moreover, in cytotrophoblasts, increased sFlt-1 mRNA expression and elevated sFlt-1 production were induced by hypoxic stimulation. Notably, hypoxia-induced elevation of sFlt-1 secretion from the cytotrophoblasts was inhibited by silencing the HIF-2α, but not HIF-1α mRNA. These findings suggest that hypoxia-induced activation of HIF-2α is essential for the increased production of sFlt-1 proteins in trophoblasts. Targeting the HIF-2α may be a novel strategy for the treatment of preeclampsia.
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