病理性妊娠中坏死性下垂的作用:机制和治疗机会

IF 2.9 3区 医学 Q3 IMMUNOLOGY
Lidan He , Shan Zheng , Feng Zhan , Na Lin
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引用次数: 0

摘要

坏死坏死是一种独特的程序性细胞死亡形式,在机制上不同于凋亡性焦亡和自噬,其特征是受体相互作用蛋白激酶(RIPK1/RIPK3)及其下游效应物,混合谱系激酶结构域样蛋白(MLKL)的激活。这种程序性细胞死亡途径是炎症反应的重要介质,并与多种病理条件的发病机制有关。最近的证据表明,失调的坏死性下垂与严重妊娠并发症的发病机制有关,包括先兆子痫(PE)、胎儿生长受限(FGR)、复发性自然流产(RSA)和妊娠糖尿病(GDM)。在这些疾病中,坏死性上垂症通过多种相互关联的机制促进胎盘功能障碍:促炎细胞因子级联扩增、异常免疫激活、质膜完整性破坏以及随后的组织损伤。这些与妊娠相关的病理一致表现出坏死的特征升高,与不良的母胎结局相关。这篇综述综合了目前对坏死性上睑下垂的分子机制的理解,特别强调了它在妊娠相关疾病的发病机制中的关键作用。此外,我们批判性地评估了靶向坏死性坏死信号轴的治疗潜力,为开发靶向干预措施以改善复杂妊娠的临床结果提供了新的视角。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The role of necroptosis in pathological pregnancies: Mechanisms and therapeutic opportunities
Necroptosis, a distinctive form of programmed cell death differs mechanistically from apoptosis pyroptosis, and autophagy, is characterized by the activation of receptor-interacting protein kinases (RIPK1/RIPK3) and their downstream effector, mixed lineage kinase domain-like protein (MLKL). This programmed cell death pathway serves as a crucial mediator of inflammatory responses and has been implicated in the pathogenesis of diverse pathological conditions. Recent evidence has implicated dysregulated necroptosis in the pathogenesis of severe pregnancy complications, including preeclampsia (PE), fetal growth restriction (FGR), recurrent spontaneous abortion (RSA), and gestational diabetes mellitus (GDM). In these disorders, necroptosis promotes placental dysfunction through multiple interconnected mechanisms: amplification of pro-inflammatory cytokine cascades, aberrant immune activation, disruption of plasma membrane integrity, and subsequent tissue injury.These pregnancy-related pathologies consistently demonstrate elevated necroptotic signatures, correlating with adverse maternal-fetal outcomes. This comprehensive review synthesizes current understanding of the molecular mechanisms underlying necroptosis, with particular emphasis on its pivotal role in the etiopathogenesis of pregnancy-related disorders. Furthermore, we critically evaluate the therapeutic potential of targeting the necroptotic signaling axis, providing novel perspectives for developing targeted interventions to improve clinical outcomes in complicated pregnancies.
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来源期刊
CiteScore
6.30
自引率
5.90%
发文量
162
审稿时长
10.6 weeks
期刊介绍: Affiliated with the European Society of Reproductive Immunology and with the International Society for Immunology of Reproduction The aim of the Journal of Reproductive Immunology is to provide the critical forum for the dissemination of results from high quality research in all aspects of experimental, animal and clinical reproductive immunobiology. This encompasses normal and pathological processes of: * Male and Female Reproductive Tracts * Gametogenesis and Embryogenesis * Implantation and Placental Development * Gestation and Parturition * Mammary Gland and Lactation.
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