Role of ARID1A in the Regulation of Human Trophoblast Migration and Invasion

2021 ◽  
Author(s):  
Meiyuan Jin ◽  
Shouying Xu ◽  
Jiayong Li ◽  
Lu Li ◽  
Chao Tang
Keyword(s):  
Migration And Invasion ◽  
Human Trophoblast ◽  
Trophoblast Migration

scholarly journals STX2 Promotes Trophoblast Growth, Migration, and Invasion Through Activation of the PI3K-AKT Pathway in Preeclampsia

2021 ◽  
Vol 9 ◽  
Author(s):  
Yan Li ◽  
Xian-li Sun ◽  
Chun-ling Ma ◽  
Chao Li ◽  
Ying Zhan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Gain Of Function ◽  
Human Trophoblast ◽  
Pi3k Inhibitor Ly294002 ◽  
Akt Activation ◽  
A Subunit ◽  
Human Trophoblast Cells

ObjectivesAbnormal trophoblast behaviors during pregnancy contribute to the development of preeclampsia (PE). Syntaxin2 (STX2) has been shown to be a crucial epithelial mediator in numerous diseases. However, the functions of STX2 and the mechanisms underlying its role in PE remain largely unknown. The aim of this study was to explore the role of STX2 on trophoblast biology and unravel the molecular mechanisms that contribute to the development and progression of PE.Materials and MethodsWe first compared the expression of STX2 in placental tissues from women with PE and women with normal pregnancies. Then, we investigated the role of STX2 on trophoblast proliferation, migration and invasion in HTR-8/SVneo and primary human trophoblast cells by loss or gain of function experiments. In addition, co-immunoprecipitation, pulldown and immunofluorescence assays were performed to investigate the co-localization of STX2 with other proteins, and to help clarify the mechanisms underlying STX2-mediated functions on trophoblasts.ResultsWe demonstrated that STX2 expression was downregulated in placental tissues of women with PE compared with those from normal pregnancies. Loss and gain of function experiments further confirmed a role for STX2 in cell proliferation, migration and invasion in trophoblasts. By co-immunoprecipitation, pulldown and immunofluorescence co-localization assays, we revealed that STX2 selectively interacted with p85, a subunit of PI3K, and directly recruited p85 to the cytomembrane, thereby activating the AKT signaling pathway. We further demonstrated that the AKT activation was abolished by the use of a PI3K inhibitor (LY294002), which negatively affected STX2-mediated functions on trophoblasts.ConclusionAll together, our findings point to a crucial role for STX2 in PE progression. Our new insights also suggest that STX2 may be a potential diagnostic tool and a novel therapeutic target for treating PE.

Role of autophagy process in vascular remodeling and oxidized LDL effect in first trimester trophoblast migration and invasion.

Placenta ◽  
2021 ◽  
Vol 112 ◽  
pp. e52
Author(s):  
Lorena Carvajal ◽  
Cantin Claudette ◽  
Gabriela Arenas ◽  
Susana Contreras-Duarte ◽  
Jaime Gutierrez ◽  
...  
Keyword(s):  
Vascular Remodeling ◽  
Oxidized Ldl ◽  
First Trimester ◽  
Migration And Invasion ◽  
Trophoblast Migration

Down-regulation of CCR7 via AKT pathway and GATA2 inactivation suppressed trophoblast migration and invasion in recurrent spontaneous abortion†

2019 ◽  
Author(s):  
Xiaorui Luan ◽  
Shang Li ◽  
Jun Zhao ◽  
Junyu Zhai ◽  
Xiaojing Liu ◽  
...  
Keyword(s):  
Spontaneous Abortion ◽  
Functional Role ◽  
Underlying Mechanism ◽  
Recurrent Spontaneous Abortion ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Control Group ◽  
Protein Abundance ◽  
Trophoblast Migration

Abstract The underlying mechanism of the chemokine-C receptor 7 (CCR7) that leads to aberrant trophoblast migration and invasion in recurrent spontaneous abortion (RSA) remains unknown. CCR7 is considered crucial for migration and invasion and has been associated with the risk of miscarriage. However, the functional role of CCR7 in RSA is not fully understood. Our study found that CCR7 mRNA and protein abundance were significantly decreased in the villous from RSA patients compared with healthy controls. Knockdown of CCR7 caused a significant reduction of migration and invasion in JAR and JEG-3 cells. Meanwhile, CCR7 functioned as a positive upstream factor of the AKT pathway contributing to the expression of GATA2, promoting trophoblast migration, and invasion via MMP2. Notably, a decreased abundance of CCR7 was positively correlated with the phosphorylation of AKT and with an abundance of GATA2 and MMP2 in human villous specimens of RSA compared with the control group. CCL19, a ligand of CCR7, could promote trophoblast migration and invasion by activating the deregulation of the CCR7-mediated pathway in RSA. We are convinced that CCR7 and its downstream factors may be possible mechanisms for the pathogenesis of RSA.

Leptin is involved in human trophoblast migration and invasion

Placenta ◽  
2015 ◽  
Vol 36 (4) ◽  
pp. 490
Author(s):  
A. Toro ◽  
R. Sampayo ◽  
A. Pérez-Pérez ◽  
B. Maskin ◽  
V. Sánchez-Margalet ◽  
...  
Keyword(s):  
Migration And Invasion ◽  
Human Trophoblast ◽  
Trophoblast Migration

Acetylcholine ameliorated TNF-α-induced primary trophoblast malfunction via muscarinic receptors†

2020 ◽  
Vol 103 (6) ◽  
pp. 1238-1248
Author(s):  
Zheng Wang ◽  
Adoulaye Issotina Zibrila ◽  
Shuhua Liu ◽  
Gongxiao Zhao ◽  
Yubei Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Muscarinic Receptors ◽  
Caspase 3 ◽  
Migration And Invasion ◽  
Vagal Activity ◽  
Trophoblast Cells ◽  
Human Trophoblast ◽  
Tnf Α

Abstract Oxidative stress and apoptosis of trophoblasts are involved in preeclampsia (PE). Numerous studies have shown that acetylcholine (ACh), the principal vagal neurotransmitter, plays a crucial role in attenuating oxidative stress, inflammation, and apoptosis in a variety of human diseases. However, the role of ACh in PE management remains unclear. Here, we aimed to determine the effects of ACh on TNF-α-treated human primary trophoblast cells. Western blotting, CCK-8, DHE, TUNEL immunofluorescence staining, transwell assays, and wound-healing assays were performed to evaluate the role of ACh in vitro. We found that both TNF-α expression and the apoptotic index were higher in placentas from preeclamptic women than in normal placentas. TNF-α enhanced oxidative stress and increased the number of TUNEL-positive nuclei, Bax/Bcl-2 ratio, and the cleaved caspase-3/caspase-3 ratio while decreasing cell viability in primary human trophoblast cells. TNF-α promoted cell migration and invasion. PDTC, a selective NF-κB inhibitor, significantly blunted TNF-α-induced effects. ACh treatment attenuated oxidative stress and apoptosis while further promoting migration and invasion of TNF-α-treated primary trophoblast cells. The effects of ACh could be reversed by the muscarinic receptor antagonist atropine. Overall, our findings indicate that ACh significantly ameliorates TNF-α-induced oxidative stress and apoptosis of human primary trophoblast cells via muscarinic receptors. This is the first time that the improvement of vagal activity served as a therapeutic strategy for PE-like trophoblasts, suggesting its potential value in clinical practice.

scholarly journals Role of Rho GTPases in Human Trophoblast Migration Induced by IGFBP11

2012 ◽  
Vol 86 (1) ◽  
Author(s):  
Jessica Saso ◽  
Sarah-Kim Shields ◽  
Yufeng Zuo ◽  
Chandan Chakraborty
Keyword(s):  
Rho Gtpases ◽  
Human Trophoblast ◽  
Trophoblast Migration

scholarly journals Regulation of the Matricellular Proteins CYR61 (CCN1) and NOV (CCN3) by Hypoxia-Inducible Factor-1α and Transforming-Growth Factor-β3 in the Human Trophoblast

Endocrinology ◽  
2010 ◽  
Vol 151 (6) ◽  
pp. 2835-2845 ◽  
Author(s):  
Nadine Wolf ◽  
Wei Yang ◽  
Caroline E. Dunk ◽  
Isabella Gashaw ◽  
Stephen J. Lye ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Extravillous Trophoblast ◽  
Migration And Invasion ◽  
Ccn Proteins ◽  
Low Oxygen ◽  
Trophoblast Cells ◽  
Human Trophoblast ◽  
Placental Perfusion ◽  
Hypoxia Inducible Factor 1Α ◽  
Trophoblast Migration

It is known that a hypoxic environment is critical for trophoblast migration and invasion and is fundamental for appropriate placental perfusion. Because cysteine-rich 61 (CYR61, CCN1) and nephroblastoma overexpressed (NOV, CCN3) are expressed in the extravillous trophoblast and expression levels are deregulated in preeclampsia, we investigated their regulation properties in first-trimester placental explants and in JEG3 choriocarcinoma cells upon a physiological low oxygen tension of 1–3%. In placental explants, both proteins were expressed in the extravillous trophoblast cells and were increased upon hypoxia. JEG3 cells revealed a significant up-regulation of CYR61 and NOV intracellular as well as secreted protein upon hypoxic treatment accompanied by the stabilization of the hypoxia-inducible factor-1α (HIF-1α). Treatment with dimethyloxalylglycine to mimic hypoxia and silencing of HIF-1α using small interfering RNA revealed that only the increase in intracellular protein expression seems to be dependent on HIF-1α but obviously not the secretion process. Moreover, recombinant TGF-β3 was able to further enhance the amount of intracellular CCN proteins as well as secreted CYR61 levels under hypoxia. These results indicate that low oxygen levels trigger elevation of intracellular as well as secreted CYR61 and NOV protein probably in two independent pathways. Addition of recombinant CYR61 and NOV proteins increases migration as well as invasion properties of JEG3 trophoblast cells, which strengthen their role in supporting trophoblast migration invasion properties. In summary, CYR61 and NOV are regulated by HIF-1α and TGF-β3 in the trophoblast cell line JEG3, and their enhanced secretion could be implicated in appropriate placental invasion.

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