Role of IGF2BP3 in trophoblast cell invasion and migration.

Role of IGF2BP3 in trophoblast cell invasion and migration.
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IGF2BP3 在滋养层细胞侵袭和迁移中的作用

DOI:
10.1038/cddis.2013.545
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发表时间:
2014-01-23
影响因子:
9
通讯作者:
--
中科院分区:
生物学1区
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--
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胰岛素样生长因子-2 mRNA结合蛋白3(IGF 2BP 3)是一个高度保守的蛋白质家族成员,在胎盘、睾丸和各种癌症中特异性表达,但在正常成人组织中几乎检测不到。IGF 2BP 3在RNA稳定和翻译中具有重要作用,特别是在人类和小鼠胚胎发生的早期阶段。胎盘是哺乳动物生殖过程中不可缺少的器官,它连接发育中的胎儿和子宫壁,负责营养吸收、废物排出和气体交换。胎儿在母体子宫腔中的发育依赖于功能特化的滋养细胞。IGF 2BP 3在胎盘发育过程中是否在滋养层分化中起作用尚未研究。结果显示,IGF 2BP 3在早孕期胎盘绒毛组织中高表达,尤其是在细胞滋养层细胞(CTB)和滋养层柱中,而在孕晚期胎盘绒毛组织中IGF 2BP 3表达水平较低。此外,IGF 2BP 3在先兆子痫(PE)胎盘中的表达水平显著低于胎龄匹配的正常胎盘。IGF 2BP 3在人滋养层细胞分化中的作用通过体外细胞侵袭和迁移测定和离体外植体培养模型显示。我们的数据支持IGF 2BP 3在促进滋养细胞侵袭中的作用,并提示IGF 2BP 3的异常表达可能与PE的病因学有关。
The insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3) is a member of a highly conserved protein family that is expressed specifically in placenta, testis and various cancers, but is hardly detectable in normal adult tissues. IGF2BP3 has important roles in RNA stabilization and translation, especially during early stages of both human and mouse embryogenesis. Placenta is an indispensable organ in mammalian reproduction that connects developing fetus to the uterine wall, and is responsible for nutrient uptake, waste elimination and gas exchange. Fetus development in the maternal uterine cavity depends on the specialized functional trophoblast. Whether IGF2BP3 plays a role in trophoblast differentiation during placental development has never been examined. The data obtained in this study revealed that IGF2BP3 was highly expressed in human placental villi during early pregnancy, especially in cytotrophoblast cells (CTBs) and trophoblast column, but a much lower level of IGF2BP3 was detected in the third trimester placental villi. Furthermore, the expression level of IGF2BP3 in pre-eclamptic (PE) placentas was significantly lower than the gestational age-matched normal placentas. The role of IGF2BP3 in human trophoblast differentiation was shown by in vitro cell invasion and migration assays and an ex vivo explant culture model. Our data support a role of IGF2BP3 in promoting trophoblast invasion and suggest that abnormal expression of IGF2BP3 might be associated with the etiology of PE.
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