1] College of Life Sciences, Beijing Normal University, Beijing 100875, China [2] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100039, China.
Cell Death Dis. 2014 Jan 23;5(1):e1025. doi: 10.1038/cddis.2013.545.
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.
胰岛素样生长因子 2 mRNA 结合蛋白 3（IGF2BP3）是一个高度保守的蛋白家族成员，特异性表达于胎盘、睾丸和各种癌症组织中，而在正常成人组织中几乎检测不到。IGF2BP3 在 RNA 稳定和翻译中发挥重要作用，尤其是在人和小鼠胚胎发育的早期阶段。胎盘是哺乳动物生殖过程中不可或缺的器官，它将发育中的胎儿与子宫壁连接起来，负责营养物质的摄取、废物的清除和气体交换。胎儿在母体子宫腔中的发育依赖于特化的功能性滋养层。IGF2BP3 是否在胎盘发育过程中的滋养层分化中发挥作用尚未被研究。本研究获得的数据表明，IGF2BP3 在妊娠早期的人胎盘绒毛中高度表达，特别是在细胞滋养层细胞（CTBs）和滋养层柱中，但在妊娠晚期的胎盘绒毛中检测到的 IGF2BP3 水平要低得多。此外，子痫前期（PE）胎盘组织中 IGF2BP3 的表达水平明显低于与胎龄相匹配的正常胎盘。通过体外细胞侵袭和迁移实验以及离体组织培养模型证明了 IGF2BP3 在人滋养层分化中的作用。我们的数据支持 IGF2BP3 在促进滋养层侵袭中的作用，并表明 IGF2BP3 的异常表达可能与 PE 的病因有关。
