BTN3A2 interacted with MFGE8 to alleviate preeclampsia by promoting ferroptosis and inhibiting angiogenesis

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-03-25 DOI:10.1016/j.lfs.2025.123584

Xi Yuan , Qi Wang , Caihong Hu , Wenjing Yong , Ping Li

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引用次数: 0

Abstract

Aims

Preeclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality and is characterized by placental ischemia. Angiogenic disorders and ferroptosis are key mechanisms in PE; however, their relationship remains unclear. The butyrophilin 3A (BTN3A) family member BTN3A2 is involved in the progression of many cancers; however, its role in PE angiogenesis and ferroptosis is unclear. In this study, we investigated the role of BTN3A2 in PE angiogenesis and ferroptosis.

Materials and methods

Placental tissues were collected from healthy individuals and PE patients to explore the correlation between ferroptosis and angiogenesis. Human umbilical vein endothelial cells (HUVECs) were subjected to hypoxia, ferrostatin-1, Erastin, and gene manipulations (oe-BTN3A2, si-BTN3A2, and si-milk factor-globule-EFG factor 8 (MFGE8)) to elucidate the underlying mechanisms. Finally, a rat model of PE was established by intraperitoneal injection of Nomega-nitro-L-arginine methyl ester to verify the effects of BTN3A2 on angiogenesis.

Key findings

Placental ferroptosis was negatively correlated with angiogenesis in PE. Clone number, migration, and tube number decreased in HUVECs after hypoxic exposure, and these effects were reversed by ferrostatin-1. BTN3A2 was increased in PE placentae and inhibited the viability of hypoxic HUVECs by inducing ferroptosis. Mechanistically, BTN3A2 interacted with MFGE8, and BTN3A2 promoted hypoxia-induced ferroptosis in HUVECs by downregulating MFGE8. Additionally, BTN3A2 knockdown promoted placental angiogenesis and improved the prognosis in PE rats.

Significance

BTN3A2 interacted with MFGE8 to alleviate PE by promoting ferroptosis and inhibiting angiogenesis. Therefore, it may serve as a potential therapeutic target for the diagnosis and treatment of PE.

Abstract Image

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BTN3A2与MFGE8相互作用，通过促进铁下垂和抑制血管生成来缓解子痫前期

目的子痫（PE）是孕产妇和围产期发病率和死亡率的主要原因，其特征是胎盘缺血。血管生成障碍和铁下垂是PE的关键机制；然而，他们的关系仍不清楚。嗜丁酸蛋白3A （BTN3A）家族成员BTN3A2参与许多癌症的进展；然而，其在PE血管生成和铁下垂中的作用尚不清楚。在这项研究中，我们研究了BTN3A2在PE血管生成和铁下垂中的作用。材料和方法收集健康个体和PE患者的胎盘组织，探讨铁下垂与血管生成的关系。研究人员对人脐静脉内皮细胞（HUVECs）进行了缺氧、他汀-1、Erastin和基因操作（e- btn3a2、si-BTN3A2和si-乳因子-球蛋白- efg因子8 (MFGE8)），以阐明其潜在机制。最后，通过腹腔注射诺米加-硝基- l -精氨酸甲酯建立大鼠PE模型，验证BTN3A2对血管生成的影响。PE患者胎盘铁下垂与血管生成呈负相关。缺氧暴露后HUVECs的克隆数、迁移量和管数减少，而铁抑素-1可以逆转这些影响。BTN3A2在PE胎盘中升高，并通过诱导铁下垂抑制缺氧huvec的活力。在机制上，BTN3A2与MFGE8相互作用，BTN3A2通过下调MFGE8促进缺氧诱导的HUVECs铁凋亡。此外，BTN3A2敲低可促进PE大鼠胎盘血管生成，改善预后。btn3a2与MFGE8相互作用，通过促进铁下垂和抑制血管生成来缓解PE。因此，它可能成为PE诊断和治疗的潜在治疗靶点。

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.