滋养层
胎盘形成
基因敲除
细胞生物学
下调和上调
细胞迁移
厌氧糖酵解
糖酵解
基因沉默
信使核糖核酸
生物
化学
细胞
胎盘
内分泌学
基因
生物化学
新陈代谢
胎儿
遗传学
怀孕
作者
Ling Song,Xinying Zhao,Jiaxi Chen,Chunxiang Cao,Hongyan Tang,Lianxiu Li,Haijing Dong,Yukui Zhang,Zhaoxia Qu,Xiaodan Chu,Man Guo
摘要
Insufficient trophoblast migration and impaired uterine spiral artery remodeling are implicated in the pathogenesis of preeclampsia, contributing to inadequate placentation. However, the molecular mechanism underlying this process remains unclear. Aerobic glycolysis, which produces substantial lactate, is crucial for establishing a favorable microenvironment for early uterine preparation and supporting embryo implantation and trophoblast migration. In the present study, we have demonstrated that SORBS2, an RNA-binding protein, regulated aerobic glycolysis and significantly improved trophoblast migration in vitro. Our results showed that SORBS2 expression was significantly reduced in human PE placentas and in trophoblasts during hypoxia. Overexpression of SORBS2 enhanced cell proliferation and migration, whereas knockdown of SORBS2 decreased these functions in HTR-8/SVneo cells. Mechanistic studies have demonstrated that SORBS2 directly interacts with the 3' untranslated regions (UTRs) of key glycolysis-related genes, specifically HK2. This interaction results in enhanced stability of HK2 and activation of glycolysis. Moreover, silencing HK2 abrogated the enhancement of proliferation and migration of HTR-8/SVneo cells induced by SORBS2. In conclusion, our findings suggest that the downregulation of SORBS2 may contribute to the pathogenesis of preeclampsia by regulating mRNA stability and inhibiting trophoblast migration during placentation.
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