Expression of SOX2, NANOG and OCT4 in a mouse model of lipopolysaccharide-induced acute uterine injury and intrauterine adhesions.
Expression of SOX2, NANOG and OCT4 in a mouse model of lipopolysaccharide-induced acute uterine injury and intrauterine adhesions.
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DOI：
10.1186/s12958-017-0234-9
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发表时间：
2017-03-03
期刊：
影响因子：
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通讯作者：
Zhou M
中科院分区：
文献类型：
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作者：
Xiao L;Song Y;Huang W;Yang S;Fu J;Feng X;Zhou M
炎症介导的子宫内膜损伤激活被认为在宫内粘连（IUA）的发病机制中起决定性作用。由于从子宫内膜中分离出了人子宫内膜干细胞，子宫内膜疾病的干细胞理论成为研究的热点。性别决定区Y-box2 （SOX2）、Nanog homebox （Nanog）和八聚体结合蛋白（OCT4）这三个转录因子在维持干细胞的多能性和自我更新中起着关键作用，它们可能与子宫内膜的损伤或修复过程有关。我们旨在研究SOX2、NANOG和OCT4在腹腔注射脂多糖（LPS）致急性子宫损伤小鼠模型中的表达，并分析其在IUA妇女子宫内膜中的变化。分别于单次LPS或PBS注射后0 h、6 h、12 h、18 h、24 h采集小鼠子宫角。同时，我们招募宫腔镜诊断为IUA的女性19例，无疾病的女性16例作为对照组。采集子宫内膜组织样本。采用实时荧光定量聚合酶链反应和Western blotting检测SOX2、NANOG和OCT4的表达。急性子宫损伤小鼠模型6 h NANOG、12 h SOX2、OCT4较注射前或注射PBS前明显升高。NANOG在6 h达到表达高峰，而SOX2和OCT4在LPS处理后12 h达到表达高峰。与对照组相比，IUA患者子宫内膜中NANOG mRNA和蛋白的表达明显升高。多能因子SOX2、NANOG和OCT4在lps诱导的急性子宫损伤小鼠模型中的表达升高。NANOG较早达到峰值，其次是其他两个因素，然后才回到基线水平。IUA患者子宫内膜NANOG过表达，而SOX2和OCT4不表达。它们可能参与IUA的形成或恢复，在IUA发病机制中的作用有待进一步研究。
Activation of inflammation-mediated endometrial injury is suggested to play a decisive role in pathogenesis of intrauterine adhesion (IUA). The stem cell theory of endometrial diseases has been given a hotspot, in that human endometrial stem cells have been isolated from the endometrium. Three transcription factors that play key roles in maintaining pluripotency and self-renewal in stem cells are sex-determining region Y-box2 (SOX2), Nanog homebox (NANOG), and octamer-binding protein (OCT4), which may be responsible for the damage or repair process of uterine endometrium. We aim to investigate the expression of SOX2, NANOG and OCT4 in a mouse model of acute uterine injury induced by peritoneal injection of lipopolysaccharide (LPS) and also analyze their changes in endometrium of women with IUA. The mouse uterine horns were collected at 0 h, 6 h, 12 h, 18 h or 24 h after a single dose of LPS or PBS injection. Meanwhile, we recruited 19 women with IUA diagnosed by hysteroscopy and 16 disease-free women as control group. Endometrial tissue samples were collected. SOX2, NANOG, and OCT4 expression were analyzed with Quantitative Real-time Polymerase Chain Reaction and Western blotting assay. In a mouse model of acute uterine injury, there was significant upregulation of NANOG at 6 h, SOX2 and OCT4 at 12 h compared with the values before injection or PBS injection. NANOG expression reached a peak at 6 h, while SOX2 and OCT4 peaked later at 12 h after LPS treatment. NANOG mRNA and protein expressions were significantly higher in endometrium of IUA patients compared to those of the control group. Expression of pluripotency factors SOX2, NANOG and OCT4 increased in a mouse model of LPS-induced acute uterine injury. NANOG peaked earlier followed by the other two factors before returning to baseline levels. NANOG but not SOX2 and OCT4 expression was overexpressed in the endometrium of women with IUA. They may be involved in the formation or restoration of IUA, and their roles in pathogenesis of IUA need to be further studied.