Decreased USP2a Expression Inhibits Trophoblast Invasion and Associates With Recurrent Miscarriage.
Decreased USP2a Expression Inhibits Trophoblast Invasion and Associates With Recurrent Miscarriage.
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USP2a 表达减少可抑制滋养层细胞侵袭并与复发性流产相关
DOI：
10.3389/fimmu.2021.717370
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发表时间：
2021
影响因子：
7.3
通讯作者：
Yin T
中科院分区：
文献类型：
--
作者：
Wang J;Ding J;Zhang S;Chen X;Yan S;Zhang Y;Yin T
胎盘的适当发育包括滋养层细胞的迁移、侵袭、增殖和凋亡，对于建立和维持成功的妊娠至关重要。泛素特异性蛋白酶2a（USP 2a）调节多种肿瘤细胞的转移过程。然而，没有已知的研究集中在探索USP 2a对滋养细胞的影响及其在复发性流产（RM）病因中的可能机制。在本研究中，我们首先检测了RM患者胎盘绒毛组织中USP 2a mRNA水平和蛋白水平的下降。体外实验证实，USP 2a的过表达促进了人滋养层细胞的增殖、迁移、侵袭，而USP 2a的敲低抑制了这些过程。在机制上，USP 2a激活PI 3 K/Akt/GSK 3 β信号通路以促进β-catenin的核转位，并进一步激活滋养层中的上皮-间充质转化（EMT）。此外，转化生长因子-β（TGF-β）上调滋养细胞中USP 2a的表达。有趣的是，M2巨噬细胞分泌TGF-β诱导滋养层迁移和侵袭，抗TGF-β抗体减轻了这种作用。总的来说，这项研究表明，USP 2a调节滋养层细胞的侵袭和异常USP 2a的表达可能会导致异常的滋养层细胞的侵袭，从而有助于RM。
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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DOI：
10.1016/j.fct.2016.06.023
发表时间：
2016-12
期刊：
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
影响因子：
--
作者：
Brooks SA;Martin E;Smeester L;Grace MR;Boggess K;Fry RC
通讯作者：
Fry RC
影响因子：
0.7
作者：
Angela Nieto, M.
通讯作者：
Angela Nieto, M.
影响因子：
7.3
作者：
Chambers M;Rees A;Cronin JG;Nair M;Jones N;Thornton CA
通讯作者：
Thornton CA
M2巨噬细胞源性G-CSF通过激活PI3K/Akt/Erk1/2通路促进滋养层细胞EMT、侵袭和迁移介导正常妊娠
影响因子：
5.3
作者：
Ding J;Yang C;Zhang Y;Wang J;Zhang S;Guo D;Yin T;Yang J
通讯作者：
Yang J
影响因子：
4.8
作者：
da Silva, Sabrina Daniela;Cunha, Isabela Werneck;Graner, Edgard
通讯作者：
Graner, Edgard