Gene Expression of Pregnancy Neutrophils Differs for Protease versus Lipopolysaccharide Stimulation.
Gene Expression of Pregnancy Neutrophils Differs for Protease versus Lipopolysaccharide Stimulation.
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DOI：
10.3390/ijms23094924
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发表时间：
2022-04-28
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
在先兆子痫中广泛浸润母体全身血管的中性粒细胞表达蛋白酶激活受体1（PAR-1），但仅在妊娠期间表达。中性粒细胞的反应通常被认为是非特异性的，但是PAR-1的妊娠特异性表达可能导致妊娠特有的基因表达谱，这可能有助于解释为什么先兆子痫中的母体炎症反应是全身性的而不是局部的。我们试图确定，如果由蛋白酶和细菌脂多糖（LPS）刺激，妊娠中性粒细胞的基因表达是否会有所不同。我们从妊娠30周的正常孕妇中分离中性粒细胞，并将其与弹性蛋白酶或LPS培养。我们使用弹性蛋白酶，因为它是一种在先兆子痫妇女中升高的蛋白酶，它通过PAR-1激活妊娠中性粒细胞。从嗜中性粒细胞中分离RNA用于转录组测序。我们发现了基因表达谱的许多差异。例如，暴露于弹性蛋白酶导致比LPS多三倍的独特表达基因，并且弹性蛋白酶的显著差异上调和下调基因的数量更大。经典途径的分析揭示了先天免疫的相似性，但也存在差异。LPS处理丰富了更多的途径，但弹性蛋白酶在每个途径中激活了更多的基因。弹性蛋白酶处理丰富了MAPK信号通路，而LPS没有。这是重要的，因为MAPK是转录反应的关键介导剂。这些发现表明，蛋白酶刺激妊娠中性粒细胞的结果与LPS刺激不同，这可能有助于解释为什么先兆子痫的无菌炎症反应是全身性的，并且是妊娠特有的。
Neutrophils, which extensively infiltrate maternal systemic blood vessels in preeclampsia, express protease-activated receptor 1 (PAR-1) but only during pregnancy. Neutrophils are generally considered to be non-specific in their response, but the pregnancy-specific expression of PAR-1 could result in a gene expression profile unique to pregnancy, which could help explain why the maternal inflammatory response in preeclampsia is systemic rather than localized. We sought to determine if gene expression of pregnancy neutrophils would differ if stimulated by a protease versus bacterial lipopolysaccharide (LPS). We isolated neutrophils from normal pregnant women at 30 weeks’ gestation and cultured them with elastase or LPS. We used elastase because it is a protease elevated in women with preeclampsia, and it activates pregnancy neutrophils via PAR-1. RNA was isolated from the neutrophils for sequencing of the transcriptomes. We discovered many differences in the gene expression profiles. For example, exposure to elastase resulted in three times more uniquely expressed genes than LPS, and the number of significantly differentially upregulated and downregulated genes was greater for elastase. Analysis of canonical pathways revealed similarities for innate immunity but also differences. LPS treatment enriched more pathways, but elastase activated more genes in each pathway. Elastase treatment enriched the MAPK signaling pathway, whereas LPS did not. This is significant because MAPK is a key mediator of transcriptional responses. These findings indicate that protease stimulation of pregnancy neutrophils results in a different profile than stimulation with LPS, which may help explain why the sterile inflammatory response of preeclampsia is systemic and unique to pregnancy.
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影响因子：
2.7
作者：
Jiang, Kaiyu;Sun, Xiaoyun;Jarvis, James N.
通讯作者：
Jarvis, James N.
来自缺氧滋养层的高迁移率组 Box 1 促进先兆子痫中内皮微粒的产生和血栓形成倾向。
DOI：
10.1161/atvbaha.118.310940
发表时间：
2018-06
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Hu Y;Yan R;Zhang C;Zhou Z;Liu M;Wang C;Zhang H;Dong L;Zhou T;Wu Y;Dong N;Wu Q
通讯作者：
Wu Q
DOI：
10.1161/hypertensionaha.111.176602
发表时间：
2011-11
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Mishra N;Nugent WH;Mahavadi S;Walsh SW
通讯作者：
Walsh SW
影响因子：
9.8
作者：
Hayashi, M;Hamada, Y;Ohkura, T
通讯作者：
Ohkura, T
DOI：
10.1016/s0002-9378(98)70254-6
发表时间：
1998-07-01
影响因子：
9.8
作者：
Sacks, GP;Studena, K;Redman, CWG
通讯作者：
Redman, CWG