M2巨噬细胞来源的外泌体miR-20a-5p通过TXNIP/NLRP3轴改善产科抗磷脂综合征的滋养细胞焦亡和胎盘损伤

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-03-22 DOI:10.1016/j.lfs.2025.123561

Hongyuan Zhang , Ning Jiang , Mingyang Xu , Die Jing , Tingting Dong , Qian Liu , Qingfeng Lv , Ruiheng Huo , Pengzheng Chen , Lei Li , Xietong Wang

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引用次数: 0

摘要

产科抗磷脂综合征（OAPS）是一种与妊娠有关的并发症，其特点是抗磷脂抗体（aPLs）诱发滋养层细胞脓毒症和胎盘损伤。M2极化巨噬细胞衍生的外泌体（M2-exos）在各种自身免疫性疾病和肿瘤中发挥抗炎、免疫调节和促进生长的作用。然而，它们在 OAPS 中的作用尚不明确。因此，在本研究中，我们从 M2 巨噬细胞中分离出了 M2-exos，并研究了它们在使用 aPLs 刺激滋养层细胞后对滋养层细胞增殖、死亡、迁移、侵袭和裂解的影响。为了明确 miR-20a-5p 和硫氧还蛋白（thioredoxin-interacting protein，TXNIP）在 OAPS 中的作用，我们进行了功能增益或缺失试验，并使用 GraphPad Prism 软件对收集到的数据进行了分析，统计显著性设定为 P < 0.05.主要发现MicroRNAs（miRNAs）测序显示 miR-20a-5p 在 M2-exos 中富集，这些 M2-exos 显著缓解了 aPLs 诱导的滋养细胞功能障碍。我们的研究结果还表明，M2-exos将miR-20a-5p直接靶向滋养层细胞中的硫氧还蛋白（TXNIP），从而抑制了TXNIP/NLRP3通路，减少了滋养层细胞中的脓毒症和炎症，改善了胎盘功能和胎儿发育。意义M2-外显子通过miR-20a-5p/TXNIP/NLRP3轴改善了OAPS的妊娠结局，因此是治疗aples诱导的OAPS的一种新方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

M2 macrophage derived exosomal miR-20a-5p ameliorates trophoblast pyroptosis and placental injuries in obstetric antiphospholipid syndrome via the TXNIP/NLRP3 axis

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M2 macrophage derived exosomal miR-20a-5p ameliorates trophoblast pyroptosis and placental injuries in obstetric antiphospholipid syndrome via the TXNIP/NLRP3 axis

Aim

Obstetric antiphospholipid syndrome (OAPS) is a pregnancy-related complication characterized by trophoblast pyroptosis and placental injury induced by antiphospholipid antibodies (aPLs). M2-polarized macrophage-derived exosomes (M2-exos) exert anti-inflammatory, immunomodulatory, and growth-promoting effects in various autoimmune diseases and tumors. However, their role in OAPS is not yet clear. Therefore, in this study, we isolated M2-exos from M2 macrophages and investigated their effects on trophoblast proliferation, death, migration, invasion, and pyroptosis following stimulation using aPLs.

Main methods

First, we established an animal model of OAPS and thereafter treated the OAPS mice with exogenous M2-exos via injection through the tail vein. Then to clarify the roles of miR-20a-5p and thioredoxin-interacting protein (TXNIP) in OAPS, we performed gain- or loss-of-function assays, and used GraphPad Prism software to analyze the collected data with statistical significance set at P < 0.05.

Key findings

MicroRNAs (miRNAs) sequencing revealed the enrichment of miR-20a-5p in M2-exos, and these M2-exos significantly alleviated aPLs-induced trophoblast dysfunction. Our results also indicated that M2-exos delivered miR-20a-5p to trophoblast cells directly targeted thioredoxin-interacting protein (TXNIP), and thus suppressed the TXNIP/NLRP3 pathway, reduced pyroptosis and inflammation in trophoblast cells, and improved placental function and fetal development.

Significance

M2-exos improve pregnancy outcomes in OAPS via the miR-20a-5p/TXNIP/NLRP3 axis, and thus represent as a novel therapeutic approach for aPLs-induced OAPS.

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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.