Exploring the link between M1 macrophages and EMT of amniotic epithelial cells: implications for premature rupture of membranes

文献类型： 外文期刊

第一作者： Gao, Yuhua

作者： Gao, Yuhua;Miao, Wang;Zhang, Jingmiao;Liu, Yize;Li, Zhikun;Song, Jiaxun;Bai, Chunyu;Zhang, Yanan;Mi, Ningning;Li, Xiangchen;Gao, Yuhua;Guan, Weijun;Bai, Chunyu

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关键词： Amniotic epithelial cells; Extracellular vesicles; Macrophages; Epithelial-mesenchymal transition

期刊名称：JOURNAL OF NANOBIOTECHNOLOGY （ 影响因子：12.6； 五年影响因子：12.3 ）

ISSN：

年卷期： 2025 年 23 卷 1 期

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收录情况： SCI

摘要： BackgroundDespite increasing evidence supporting the role of an amniotic epithelial-mesenchymal transition (EMT) in the premature rupture of membranes (PROMs), it remains unclear if extracellular vesicle (EV) derived from M1 macrophages play a critical role in triggering the EMT of amniotic epithelial cells (AECs).ResultsThis study revealed that under inflammatory conditions, EV-miR-146a/155 from M1 macrophages could trigger EMTs and MMP-9 transcription in AECs, elevating the risk of PROM in both mice and humans. Introduction of EV-miR-155 led to inhibition of Ehf expression and reduced E-cadherin transcription in AECs. Meanwhile, EV-miR-146a activated the beta-catenin/Tcf7 complex to promote the transcription of Snail, MMP-9, and miR-146a/155, inducing EMTs. Subsequently, EMT induction in AECs is associated with a loss of epithelial characteristics, disruption of cellular junctions, widening of intercellular spaces, and diminished biomechanical properties of the amniotic membrane.ConclusionInflammatory stimulation prompts the polarization of macrophages in amniotic fluid into the M1 type, which subsequently secrete EVs laden with inflammatory miRNAs. These EVs trigger the EMT of AECs, causing the loss of their epithelial phenotype. Consequently, the biomechanical properties of the amnion deteriorate, ultimately leading to its rupture, posing risks relevant to pregnancy complications such as premature rupture of membranes. The results of this study provide insights into the pathogenesis of PROM and will aid in treatment development.

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