p53-mediated suppression of the SLC7 A11/GPX4 signaling pathway promotes trophoblast ferroptosis in preeclampsia

作者：Tingting Liao, Xia Xu, Guiying Wang, Jian­ying Yan · 发表于：BMC Biology · 年份：2025 · DOI：10.1186/s12915-025-02240-9 · 被引用次数：12 · 研究领域：Pregnancy and preeclampsia studies、Ferroptosis and cancer prognosis、Iron Metabolism and Disorders

BACKGROUND: Ferroptosis is an iron-dependent form of non-apoptotic cell death that occurs through increased plasma membrane phospholipid peroxidation in the context of impaired plasma membrane phospholipid peroxide repair systems. It has been reported that p53 can inhibit the expression of cysteine/glutamate reverse transporter solute carrier family 7, member 11 (SLC7A11), a key component of system Xc-, thus inhibiting cysteine uptake and promoting reactive oxygen species (ROS) accumulation as an important part of cell ferroptosis. Preeclampsia (PE) is an idiopathic hypertensive disease of pregnancy. Spiral artery insufficiency and impaired placental development are present at all stages, leading to placental hypoperfusion, ischemia, and hypoxia. However, the role of ferroptosis, particularly p53-mediated trophoblast ferroptosis, in placental dysfunction during PE remains unclear. RESULTS: In PE placental tissues, malondialdehyde (MDA) and total iron levels were elevated, and trophoblasts exhibited typical ferroptosis-associated morphological changes. Additionally, p53 mRNA and protein expression and the percentage of p53-positive cells were increased, while SLC7A11 and GPX4 mRNA and protein expression and the percentage of positive cells were decreased. VEGFR1 protein expression was upregulated, whereas VEGFA and PLGF protein expression was downregulated. p53 protein expression was negatively correlated with the expression of proteins in the SLC7A11/GPX4 signaling pathway, V...