microRNA-133b通过调控滋养细胞中TGF-β信号通路参与子痫前期发病机制的研究

Preeclampsia is a pregnancy-specific disorder and a leading cause of maternal and perinatal mortality. It is generally agreed that poor placentation resulted from defected trophoblast function plays an important role in the pathology of preeclampsia. Transforming growth receptor-β (TGF-β) has been found to be highly expressed in preeclamptic placenta and inhibit trophoblast proliferation, migaration and invasion, followed by poor remodeling of spiral arteries and onset of preeclampsia. In our study, we have found decreased expression of miR-133b in preeclamptic placenta. Overexpression of miR-133b in trophoblast induced cell proliferation and migaration, and reduced protein levels of TGFB2 and TGFBR1 in TGF-β pathway. Thus we assume that miR-133b attenuates the TGF-β signaling-mediated inhibition of trophoblast proliferation, migaration and invasion by post-transcriptional repression of TGFB2 and TGFBR1; decreased expression of miR-133b impairs trophoblast function to trigger preeclampsia. This study will use molecular biological technologies and animal experiments to find out the mechanism of miR-133b-induced trophoblast function, which may provide prognostic indicators and potential therapeutic targets for clinical trials of preeclampsia.

子痫前期作为常见的妊娠特有疾病，是引起孕产妇和围产儿死亡的重要原因，其发病的关键因素是滋养细胞功能异常导致的胎盘发育障碍。研究显示，转化生长因子TGF-β在子痫前期胎盘中表达升高，抑制了滋养细胞的增殖、迁移和侵袭等功能，继而引起胎盘血管重塑不良，导致子痫前期发生。我们已发现，miR-133b在子痫前期胎盘中表达降低；滋养细胞中高表达miR-133b可促进细胞增殖和迁移，降低TGF-β信号通路中TGFB2和TGFBR1的蛋白水平。因此我们假设，miR-133b可能通过在转录后水平靶向抑制TGFB2和TGFBR1的表达，从而削弱了TGF-β信号通路对滋养细胞增殖、迁移和侵袭等能力的抑制；miR-133b表达下降则影响了滋养细胞功能，推动子痫前期的发生。该研究拟通过分子细胞学和动物实验等技术，深入探讨miR-133b促进滋养细胞功能的分子机制，为寻找子痫前期早期预测指标和治疗靶点提供新的思路。

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