滋养层
基因敲除
上皮-间质转换
PI3K/AKT/mTOR通路
生物
细胞生物学
蛋白激酶B
细胞迁移
信号转导
胎盘
细胞凋亡
癌症研究
转移
细胞
癌症
胎儿
怀孕
生物化学
遗传学
作者
Jiayu Wang,Jinli Ding,Sainan Zhang,Xin Chen,Sisi Yan,Yan Zhang,Tailang Yin
标识
DOI:10.3389/fimmu.2021.717370
摘要
An appropriate development of the placenta consisting of trophoblast cell migration, invasion, proliferation, and apoptosis, is essential to establishing and maintaining a successful pregnancy. Ubiquitin-specific protease 2a (USP2a) regulates the processes of metastasis in multiple tumor cells. Yet, no known research has focused on exploring the effect of USP2a on trophoblasts and its possible mechanism in the pathogenies of recurrent miscarriage (RM). In this study, we first detected the decreased mRNA levels and the protein levels of USP2a in placental villous tissue samples from the RM patients. In vitro assays verified that overexpression of USP2a promoted human trophoblast proliferation, migration, invasion, whereas knockdown of USP2a inhibited these processes. Mechanistically, USP2a activated PI3K/Akt/GSK3β signaling pathway to promote nuclear translocation of β-catenin and further activated epithelial-mesenchymal transition (EMT) in the trophoblasts. Moreover, transforming growth factor-beta (TGF-β) up-regulated USP2a expression in trophoblasts. Interestingly, M2 macrophage secreted TGF-β induced trophoblast migration and invasion, and an anti-TGF-β antibody alleviated this effect. Collectively, this study indicated that USP2a regulated trophoblast invasion and that abnormal USP2a expression might lead to aberrant trophoblast invasion, thus contributing to RM.
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