Differential expression of thioredoxin binding protein-2/Txnip in human placenta: Possible involvement of hypoxia in its suppression during early pregnancy
Differential expression of thioredoxin binding protein-2/Txnip in human placenta: Possible involvement of hypoxia in its suppression during early pregnancy
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DOI：
10.1111/jog.13149
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发表时间：
2017-01-01
影响因子：
1.6
通讯作者：
Konishi, Ikuo
中科院分区：
文献类型：
--
作者：
Mogami, Haruta;Yura, Shigeo;Konishi, Ikuo
目的硫氧还蛋白结合蛋白-2 (TBP-2) 与硫氧还蛋白相互作用蛋白 (Txnip) 相同，控制细胞增殖和分化。本研究的目的是比较妊娠三个月期间人胎盘中TBP-2蛋白和mRNA的表达，并探讨缺氧在胎盘组织中这些表达变化中的作用。第二个目的是使用 TBP-2 基因破坏小鼠 (TBP-2(-/-)) 测定 TBP-2 缺陷胎盘中过氧化物酶体增殖物激活受体 (PPAR) 的基因表达。方法通过免疫组织化学、Western blot 和定量逆转录酶聚合酶链反应分析每个妊娠期的人胎盘中 TBP-2 的蛋白质和 mRNA 表达。使用人胎盘外植体培养物测试缺氧对 TBP-2 表达的影响。在TBP-2(-/-)小鼠胎盘中检测到PPAR mRNA的表达。结果TBP-2定位于合体滋养细胞和细胞滋养细胞，人胎盘中也定位于内皮细胞。它在胎盘中的表达在妊娠早期较低，在妊娠中期和晚期升高。缺氧降低了人胎盘外植体培养物中 TBP-2 mRNA 和蛋白的表达。在TBP-2(-/-)小鼠中，与野生型小鼠相比，胎盘PPAR mRNA水平显着受到抑制。结论缺氧抑制TBP-2基因表达，最终可能改变胎盘发育。
AimThioredoxin binding protein-2 (TBP-2), which is identical to thioredoxin interacting protein (Txnip), controls cellular proliferation and differentiation. The aim of the present study was to compare TBP-2 protein and mRNA expression in human placenta during the three trimesters of pregnancy and to investigate the role of hypoxia in the change of these expressions in placental tissue. A secondary objective was to determine the gene expression of peroxisome proliferator-activated receptors (PPARs) in TBP-2 deficient placenta using TBP-2 gene disrupted mice (TBP-2(-/-)).MethodsProtein and mRNA expression of TBP-2 in human placenta from each trimester were analyzed by immunohistochemistry, Western blots, and by quantitative reverse-transcriptase-polymerase chain reaction. The effect of hypoxia on TBP-2 expression was tested using an explant culture of human placenta. In TBP-2(-/-) mouse placenta, we detected PPAR mRNA expression.ResultsTBP-2 was located in syncytiotrophoblasts and cytotrophoblasts, and also in the endothelium in human placenta. Its expression in the placenta was low in the first trimester, and increased in the second and third trimesters. Hypoxia decreased TBP-2 mRNA and protein expression in human placental explant culture. In TBP-2(-/-) mice, placental mRNA levels of PPAR and were significantly suppressed compared with those in wild-type mice.ConclusionHypoxia suppresses TBP-2 gene expression, which may ultimately alter placental development.