PDF(Pubmed)
Abstract：
In patients with endometriosis, refluxed endometrial fragments evade host immunosurveillance, developing into endometriotic lesions. However, the mechanisms underlying this evasion have not been fully elucidated. N-Myc and STAT Interactor (NMI) have been identified as key players in host immunosurveillance, including interferon (IFN)-induced cell death signaling pathways. NMI levels are markedly reduced in the stromal cells of human endometriotic lesions due to modulation by the Estrogen Receptor beta/Histone Deacetylase 8 axis. Knocking down NMI in immortalized human endometrial stromal cells (IHESCs) led to elevated RNA levels of genes involved in cell-to-cell adhesion and extracellular matrix signaling following IFNA treatment. Furthermore, NMI knockdown inhibited IFN-regulated canonical signaling pathways, such as apoptosis mediated by Interferon Stimulated Gene Factor 3 and necroptosis upon IFNA treatment. In contrast, NMI knockdown with IFNA treatment activated non-canonical IFN-regulated signaling pathways that promote proliferation, including β-Catenin and AKT signaling. Moreover, NMI knockdown in IHESCs stimulated ectopic lesions\' growth in mouse endometriosis models. Therefore, NMI is a novel endometriosis suppressor, enhancing apoptosis and inhibiting proliferation and cell adhesion of endometrial cells upon IFN exposure.
摘要：
子宫内膜异位症患者，回流的子宫内膜片段逃避宿主免疫监视，发展为子宫内膜异位病变。然而,这种逃避的潜在机制尚未完全阐明。N-Myc和STATInteractor（NMI）已被确定为宿主免疫监视的关键参与者，包括干扰素（IFN）诱导的细胞死亡信号通路。由于雌激素受体β/组蛋白去乙酰化酶8轴的调节，人子宫内膜异位病变的基质细胞中的NMI水平显着降低。在永生化人子宫内膜基质细胞（IHESC）中敲除NMI导致IFNA治疗后参与细胞间粘附和细胞外基质信号传导的基因的RNA水平升高。此外，NMI敲低抑制IFN调节的经典信号通路，例如由干扰素刺激的基因因子3介导的细胞凋亡和IFNA处理后的坏死。相比之下,用IFNA处理的NMI敲低激活促进增殖的非规范IFN调节的信号通路,包括β-Catenin和AKT信号传导。此外，在小鼠子宫内膜异位症模型中，IHESC中的NMI敲除刺激异位病变的生长。因此,NMI是一种新型的子宫内膜异位症抑制剂，IFN暴露后增强子宫内膜细胞的凋亡并抑制其增殖和细胞粘附。
