CDX2 Enhances HTR-8/SVneo Trophoblast Cell Invasion by Altering the Expression of Matrix Metalloproteinases
CDX2 Enhances HTR-8/SVneo Trophoblast Cell Invasion by Altering the Expression of Matrix Metalloproteinases
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DOI：
10.1159/000363028
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发表时间：
2014-01-01
影响因子：
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通讯作者：
Lu, Qin
中科院分区：
文献类型：
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作者：
Jia, Rui-Zhe;Ding, Gui-Chun;Lu, Qin
背景/目标：滋养层细胞侵入母体子宫蜕膜对人类正常胎盘形成、妊娠建立和维持胎儿生长至关重要。多种生长因子和细胞因子与滋养层侵袭有关，但侵袭的潜在调节机制尚未完全清楚。我们前期的研究发现，在子痫前期胎盘组织中，尾部相关同源异型盒转录因子2（CDX 2）是低甲基化的。然而，CDX 2是否参与滋养层细胞侵袭尚不清楚。方法和结果：在这项研究中，我们使用过表达CDX 2的人HTR-8/SVneo细胞系研究了CDX 2的功能。细胞侵袭实验表明，CDX 2增强滋养层细胞的侵袭力。MTT法检测CDX 2对细胞增殖无明显影响。Western blot分析和实时荧光定量PCR显示，CDX 2高表达的滋养层细胞中基质金属蛋白酶-9（MMP-9）的表达水平显著升高，而基质金属蛋白酶组织抑制因子-1（TIMP-1）的表达水平显著降低。磷酸肌醇-3-激酶（PI 3 K）/Akt信号通路参与细胞增殖、迁移、转移和侵袭。我们的研究表明，抑制PI 3 K/Akt信号转导导致CDX 2表达减少。结论：CDX 2在滋养层细胞侵袭过程中可能受到PI 3 K/Akt信号通路的调控。我们的研究结果可能揭示滋养层细胞侵袭的调控机制的新见解，并可能是一个重要的贡献者，妊娠相关疾病的发病机制。版权所有（C）2014 S. Karger AG，巴塞尔
Background/Aims: The invasion of trophoblast cells into the maternal uterine decidua is critical for normal placentation, establishment of pregnancy and maintenance of fetal growth in humans. Several growth factors and cytokines have been implicated in trophoblast invasion, but the underlying regulatory mechanisms of invasion are not fully understood. Our earlier studies have found that caudal related homeobox transcription factor 2 (CDX2) is hypomethylated in human pre-eclampsia placental tissues. However, whether CDX2 is involved in trophoblast invasion was unclear. Methods and Results: In this study, we investigated CDX2 function using a human HTR-8/SVneo cell line that overexpressed CDX2. Cell invasion assays demonstrated that CDX2 enhanced trophoblast cell invasiveness. Meanwhile, MTT assays revealed that CDX2 did not affect cell proliferation. Western blot analysis and quantitative real-time PCR demonstrated that the expression level of matrix metalloproteinase-9 (MMP-9) was significantly increased, whereas the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) was markedly suppressed in the CDX2-overexpressing trophoblast cells. The phosphoinositide-3-kinase (PI3K)/Akt signaling pathway is involved in proliferation, migration, metastasis and invasion. Our study showed that inhibition of PI3K/Akt signaling led to decreased expression of CDX2. Conclusion: We concluded that CDX2 is likely regulated by the PI3K/Akt signaling pathway during trophoblast cell invasion. Our findings may reveal new insights into the regulatory mechanisms of trophoblast cell invasion and may be an important contributor to the pathogenesis of pregnancy related diseases. Copyright (C) 2014 S. Karger AG, Basel