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子痫前期中 CD14++ 和 CD16++ 单核细胞的独特基因表达模式。

Distinct gene expression patterns for CD14++ and CD16++ monocytes in preeclampsia.

机构信息

National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation, Moscow, Russia.

Peoples' Friendship University of Russia, Moscow, Russia.

出版信息

Sci Rep. 2022 Sep 14;12(1):15469. doi: 10.1038/s41598-022-19847-5.

Abstract

Preeclampsia (PE) is a serious gestational complication affecting the life of a mother and child. The immunophenotype and gene expression profile of isolated blood monocyte subpopulations of pregnant women with PE have not been studied before. In this work, we assessed changes in CD14++ and CD16++ monocyte subpopulations in PE and physiological pregnancy (n = 33). Immunophenotyping, immunomagnetic sorting of monocytes and analysis of the transcriptional profile of their genes were carried out. The percentage of classical monocytes was significantly lower, while the intermediate fraction of monocytes was significantly higher in late-onset PE compared to control. Transcriptome analysis of late-onset PE classical CD14++ monocytes revealed significant activation of inflammation mediated by chemokine and cytokine signalling pathways; apoptosis; regulation of transcription from RNA polymerase II promoter in response to stress and others. The most suppressed signalling pathways were associated with T cell activation and selection. In CD16++ monocytes of late-onset PE cases, positive regulation of cell-cell adhesion, integrin signalling pathway, blood coagulation cascade were the most activated ones. The inflammation mediated by chemokine and cytokine signalling pathway and p53 pathway were the most down-regulated in CD16++ monocytes. The obtained results indicate profound changes occurring to two most polar monocyte subpopulations in PE and their different roles in the pathogenesis of this disease.

摘要

子痫前期 (PE) 是一种严重的妊娠并发症,影响母婴生命。此前尚未研究过患有 PE 的孕妇分离血液单核细胞亚群的免疫表型和基因表达谱。在这项工作中,我们评估了 PE 和生理妊娠中 CD14++和 CD16++单核细胞亚群的变化(n=33)。进行了免疫表型、单核细胞的免疫磁珠分选和基因转录谱分析。与对照组相比,晚发型 PE 中的经典单核细胞比例显著降低,而中间单核细胞比例显著升高。对晚发型 PE 经典 CD14++单核细胞的转录组分析显示,趋化因子和细胞因子信号通路介导的炎症、细胞凋亡、对 RNA 聚合酶 II 启动子的转录调控等方面的显著激活;对压力的反应等。受抑制最明显的信号通路与 T 细胞激活和选择有关。在晚发型 PE 病例的 CD16++单核细胞中,细胞间粘附的正调控、整合素信号通路、凝血级联反应是最活跃的。趋化因子和细胞因子信号通路和 p53 通路在 CD16++单核细胞中表达下调最明显。这些结果表明,PE 中两种最极性的单核细胞亚群发生了深刻的变化,它们在这种疾病的发病机制中发挥不同的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2af9/9474473/caa5542cb333/41598_2022_19847_Fig1_HTML.jpg

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