Role of peroxiredoxin2 downregulation in recurrent miscarriage through regulation of trophoblast proliferation and apoptosis.
Role of peroxiredoxin2 downregulation in recurrent miscarriage through regulation of trophoblast proliferation and apoptosis.
复制标题
过氧化物酶2下调通过调节滋养层增殖和凋亡在复发性流产中的作用。
DOI：
10.1038/cddis.2017.301
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发表时间：
2017-06-29
影响因子：
9
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Wu F;Tian F;Zeng W;Liu X;Fan J;Lin Y;Zhang Y
Peroxiredoxin（Prdx）2是一种抗氧化蛋白，其利用其氧化还原敏感的半胱氨酸基团来还原过氧化氢分子并保护细胞免受活性氧（ROS）的氧化损伤。然而，其在母胎界面滋养层细胞中的功能尚未阐明。在这项研究中，显着较低的Prdx 2表达被发现在妊娠早期绒毛细胞滋养细胞的复发性流产（RM）患者比健康对照组的细胞滋养细胞。此外，Prdx 2敲低抑制滋养层细胞的增殖并增加其凋亡。其原因可能是Prdx 2敲低后细胞ROS水平增加，随后可能导致磷酸化p53（p-p53）和p38-MAPK/p21表达增加。Prdx 2基因敲低也损害了Forskolin诱导的BeWo细胞融合。生物信息学分析确定了一个c-Myc的结合位点在Prdx 2启动子区域，染色质免疫沉淀证实，c-Myc直接结合到该位点。抑制和过度表达c-Myc分别导致Prdx 2表达减少和增加。此外，我们还发现，在RM患者的早期妊娠细胞滋养层细胞中，c-Myc表达下调，其下调还与细胞增殖抑制、细胞凋亡增加以及p21表达和p-p53/p53比值上调有关。我们的研究结果表明，Prdx 2可能在早期妊娠滋养细胞增殖和凋亡的调节中发挥重要作用，其表达由c-Myc介导。因此，这两种蛋白质可能参与RM的发病机制，并可能代表潜在的治疗靶点。
Peroxiredoxin (Prdx) 2 is an antioxidant protein that utilizes its redox-sensitive cysteine groups to reduce hydrogen peroxide molecules and protect cells against oxidative damage from reactive oxygen species (ROS). However, its function in trophoblasts at the maternal–fetal interface has not been clarified yet. In this study, significantly lower Prdx2 expression was found in the first-trimester villous cytotrophoblasts of patients with recurrent miscarriage (RM) than in cytotrophoblasts from healthy controls. Further, Prdx2 knockdown inhibited proliferation and increased apoptosis of trophoblast cells. The reason for this may be an increase in the level of cellular ROS after knockdown of Prdx2, which may subsequently lead to an increase in the expression of phosphorylated p53 (p-p53) and p38-MAPK/p21. Prdx2 knockdown also impaired the fusion of BeWo cells induced by forskolin. Bioinformatics analysis identified a c-Myc-binding site in the Prdx2 promoter region, and chromatin immunoprecipitation verified that c-Myc directly bound to a site in this locus. Suppression and overexpression of c-Myc resulted in reduction and increase of Prdx2 expression respectively. Furthermore, we demonstrated that c-Myc was downregulated in the first-trimester cytotrophoblasts of patients with RM, and its downregulation is also related with inhibited cell proliferation, increased apoptosis, as well as upregulated p21 expression and p-p53/p53 ratio. Our findings indicate that Prdx2 might have an important role in the regulation of trophoblast proliferation and apoptosis during early pregnancy, and that its expression is mediated by c-Myc. Thus, these two proteins may be involved in the pathogenesis of RM and may represent potential therapeutic targets.
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影响因子：
64.8
作者：
Bartkova, J;Horejsi, Z;Bartek, J
通讯作者：
Bartek, J
影响因子：
11.5
作者：
Bucci, B;D'Agnano, I;Vecchione, A
通讯作者：
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CpG 寡脱氧核苷酸下调胎盘脂联素并增加非肥胖糖尿病小鼠的胚胎损失。
DOI：
10.1111/aji.12515
发表时间：
2016-07
期刊：
American journal of reproductive immunology (New York, N.Y. : 1989)
影响因子：
--
作者：
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通讯作者：
Lin Y
DOI：
10.1073/pnas.1009324107
发表时间：
2010-08-31
影响因子：
11.1
作者：
Hirota, Yasushi;Acar, Nuray;Dey, Sudhansu K.
通讯作者：
Dey, Sudhansu K.
影响因子：
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作者：
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