蛋白激酶B
PI3K/AKT/mTOR通路
滋养层
组织谷氨酰胺转胺酶
生物
细胞凋亡
细胞生长
转染
分子生物学
基因敲除
下调和上调
癌症研究
男科
信号转导
细胞生物学
细胞培养
胎盘
医学
胎儿
基因
生物化学
酶
遗传学
怀孕
作者
Min Cheng,Zequn Liu,Wanqing Ji,Jie Zheng,Huiqian Zeng,Fang Guo,Ping He
出处
期刊:Gynecologic and Obstetric Investigation
[S. Karger AG]
日期:2021-01-01
卷期号:86 (3): 264-272
被引量:1
摘要
<b><i>Objectives:</i></b> The pathogenesis of preeclampsia (PE) is associated with impaired trophoblast invasion, which results in placental insufficiency. Our earlier studies demonstrated that tissue transglutaminase (tTG) is highly expressed in human PE serum. However, whether tTG participates in trophoblast invasion remains unclear. The aim of the present study was to determine the role and mechanism of tTG in regulating matrix metalloproteinase (MMP)-2/MMP-9 expression to reduce trophoblast invasiveness in PE. <b><i>Methods:</i></b> HTR-8/SVneo cells were transfected with a lentivirus vector and small interfering RNA targeting tTG. The protein level was detected by Western blotting. Cell proliferation and apoptosis were assessed by MTS and flow cytometry assays, respectively. Cell invasion was investigated by Transwell assay. In addition, the influence of tTG on PI3K and AKT mRNA levels in HTR-8/SVneo cells was evaluated using reverse transcription-quantitative PCR. <b><i>Results:</i></b> tTG-overexpression inhibited HTR-8/SVneo cell proliferation and invasion and promoted apoptosis. In addition, upregulation of tTG induced an increase of PI3K and phosphorylated AKT and a decrease of MMP-2 and MMP-9 expression. tTG-knockdown significantly promoted the proliferation and invasion of HTR-8/SVneo cells and inhibited the apoptosis. Furthermore, the PI3K expression level was reduced, and the MMP-2/MMP-9 protein levels were increased. <b><i>Conclusion:</i></b> Taken together, the present study demonstrated that tTG-overexpression inhibited HTR-8/SVneo cell invasion via reducing the expression of MMP-2 and MMP-9 by activating PI3K/AKT signaling pathway, which may lead to the occurrence or development of PE. The present data provide new insights into modulation of tTG expression as a potential therapeutic target for PE.
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