scholarly journals Smurf2 Participates in Human Trophoblast Cell Invasion by Inhibiting TGF-β Type I Receptor

2009 ◽  
Vol 57 (6) ◽  
pp. 605-612 ◽  
Author(s):  
Qing Yang ◽  
Sheng-Ping Chen ◽  
Xiao-Ping Zhang ◽  
Hongmei Wang ◽  
Cheng Zhu ◽  
...  
Keyword(s):  
Cell Invasion ◽  
Trophoblast Cell ◽  
Type I ◽  
Human Trophoblast

Myostatin increases human trophoblast cell invasion by upregulating N-cadherin via SMAD2/3-SMAD4 Signaling

2022 ◽  
Author(s):  
Faten AbdelHafez Ahmed ◽  
Christian Klausen ◽  
Hua Zhu ◽  
Peter C K Leung
Keyword(s):  
Cell Invasion ◽  
Transforming Growth Factor ◽  
Muscle Growth ◽  
Growth Control ◽  
Trophoblast Cell ◽  
Type I ◽  
Dependent Manner ◽  
Placental Development ◽  
Human Trophoblast ◽  
Protein Levels

Abstract Placental insufficiency disorders are major obstetric complications that share a common phenomenon of poor placental trophoblast cell invasion and remodeling of uterine tissues. Myostatin is a transforming growth factor (TGF)-β superfamily member well-known for its important role in muscle growth control. Myostatin is also produced in the placenta and has been shown to regulate some trophoblast functions. However, its roles in placental development are still poorly understood. In this study, we tested the hypothesis that myostatin increases trophoblast cell invasion by upregulating N-cadherin via SMAD2/3-SMAD4 signaling. Primary and immortalized (HTR8/SVneo) trophoblast cells were used as study models. Matrigel-coated transwell invasion assays were used to study the effects of recombinant human myostatin on trophoblast cell invasion. RT-qPCR and Western blot were used to measure myostatin effects on N-cadherin mRNA and protein levels, respectively. Small inhibitor molecules as well as siRNA-mediated knockdown were used to block myostatin receptor and downstream signaling, respectively. Data were analyzed either by unpaired Student T test or one-way ANOVA followed by Newman Keuls test for multiple group comparisons. Myostatin significantly increased primary and HTR8/SVneo trophoblast cell invasion. Moreover, myostatin upregulated N-cadherin mRNA and protein levels in a time dependent manner in both study models. These effects were blocked by inhibition of TGF-β type I receptors as well as siRNA-mediated knockdown of SMAD2/3 combined or common SMAD4. Importantly, myostatin-induced trophoblast cell invasion was abolished by knockdown of N-cadherin, SMAD2/3 or SMAD4. Myostatin may increase human trophoblast cell invasion by upregulating N-cadherin via SMAD2/3-SMAD4 signaling.

scholarly journals Activin A Increases Human Trophoblast Invasion by Inducing SNAIL-Mediated MMP2 Up-Regulation Through ALK4

2015 ◽  
Vol 100 (11) ◽  
pp. E1415-E1427 ◽  
Author(s):  
Yan Li ◽  
Christian Klausen ◽  
Hua Zhu ◽  
Peter C. K. Leung
Keyword(s):  
Cell Invasion ◽  
Primary Cultures ◽  
First Trimester ◽  
Activin A ◽  
Trophoblast Cell ◽  
Trophoblast Invasion ◽  
Type I ◽  
Dependent Manner ◽  
Human Trophoblast ◽  
Protein Levels

Context: Activin A increases matrix metalloproteinase (MMP) 2 expression and cell invasion in human trophoblasts, but whether the expression of MMP2 is essential for the proinvasive effect of activin A has yet to be determined. Moreover, the identity of the activin receptor-like kinase (ALK; TGF-β type I receptors) and downstream transcription factors (eg, SNAIL and SLUG) mediating the effects of activin on MMP2 expression and trophoblast cell invasion remains unknown. Objective: To elucidate the role of MMP2 in activin A-induced human trophoblast cell invasion as well as the involvement of ALK4 and SNAIL. Design: HTR8/SVneo immortalized human extravillous cytotrophoblast (EVT) cells and primary cultures of human first-trimester EVT cells were used as study models. Small interfering RNA (siRNA)-mediated knockdown approaches were used to investigate the molecular determinants of activin A-mediated functions. Main Outcome Measures: Levels of mRNA and protein were examined by reverse transcription-quantitative real-time PCR and Western blot, respectively. Cell invasiveness was measured by Matrigel-coated transwell assays. Results: Treatment of HTR8/SVneo cells with activin A increased the production of SNAIL, SLUG, and MMP2 without altering that of MMP9, TIMP1, TIMP2, TWIST, RUNX2, ZEB1, or ZEB2. Similarly, activin A up-regulated the mRNA and protein levels of SNAIL and MMP2 in primary EVT cells. Knockdown of SNAIL attenuated activin A-induced MMP2 up-regulation in HTR8/SVneo and primary EVT cells. In HTR8/SVneo cells, activin A-induced production of SNAIL and MMP2 was abolished by pretreatment with the TGF-β type I receptor (ALK4/5/7) inhibitor SB431542 or siRNA targeting ALK4, SMAD2/3, or common SMAD4. Likewise, knockdown of ALK4 or SMAD4 abolished the stimulatory effects of activin A on SNAIL and MMP2 expression in primary EVT cells. Importantly, activin A-induced HTR8/SVneo and primary EVT cell invasion were attenuated by siRNA-mediated depletion of ALK4 or MMP2. Conclusion: Activin A induces human trophoblast cell invasion by inducing SNAIL-mediated MMP2 expression through ALK4 in a SMAD2/3-SMAD4-dependent manner.

Caveolin-1 promotes trophoblast cell invasion through the focal adhesion kinase (FAK) signalling pathway during early human placental development

2019 ◽  
Vol 31 (6) ◽  
pp. 1057 ◽  
Author(s):  
Zhihui Dai ◽  
Fei Sheng ◽  
Ningxia Sun ◽  
Yixuan Ji ◽  
Qiuying Liao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Cell Invasion ◽  
Trophoblast Cell ◽  
Signalling Pathway ◽  
Placental Development ◽  
Human Trophoblast ◽  
Expression Levels ◽  
Caveolin 1

Normal implantation and placental development depend on the appropriate differentiation and invasion of trophoblast cells. Inadequate trophoblast cell invasion results in pregnancy-related disorders, which endanger both mother and fetus; however, the mechanism of early placental development has not been fully explained. In this study we conducted gene expression profile analysis using mouse placental tissues at different developmental stages (embryonic day (E)7.5, E14.5 and E19.5) using series tests of cluster (STC) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses. Focal adhesion kinase (FAK) signalling pathway-related gene expression levels were verified using quantitative reverse transcription polymerase chain reaction and western blot. The results showed that caveolin-1 (Cav1) was downregulated in the placenta of unexplained spontaneous abortion subjects compared with that of induced abortion. Furthermore, by modulating CAV1 expression levels, CAV1 was shown to promote human trophoblast cell proliferation, migration and invasion by activating the FAK signalling pathway. These results indicate that CAV1 and the FAK signalling pathway are crucial for early placental development, which sheds new light on our understanding of the mechanisms of human trophoblast cell invasion and early development of the placenta.

Activin A, B and AB increase human trophoblast cell invasion by up-regulating N-cadherin

Placenta ◽  
2013 ◽  
Vol 34 (9) ◽  
pp. A49
Author(s):  
Yan Li ◽  
Jung-Chien Cheng ◽  
Christian Klausen ◽  
Peter Leung
Keyword(s):  
Cell Invasion ◽  
Activin A ◽  
Trophoblast Cell ◽  
Human Trophoblast

Down-regulation of B2R contributes to preeclampsia by inhibiting human trophoblast cell invasion and angiogenesis

2020 ◽  
Vol 21 ◽  
pp. 14-22
Author(s):  
Yanfang Peng ◽  
Dan Liu ◽  
Zhenyu Diao ◽  
Zhiyin Wang ◽  
Hailin Ding ◽  
...  
Keyword(s):  
Cell Invasion ◽  
Trophoblast Cell ◽  
Down Regulation ◽  
Human Trophoblast

scholarly journals G protein-coupled estrogen receptor stimulates human trophoblast cell invasion via YAP-mediated ANGPTL4 expression

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jung-Chien Cheng ◽  
Lanlan Fang ◽  
Yuxi Li ◽  
Avinash Thakur ◽  
Pamela A. Hoodless ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
G Protein ◽  
Cell Invasion ◽  
Trophoblast Cell ◽  
Estrogen Signaling ◽  
Trophoblast Cells ◽  
Independent Manner ◽  
Human Trophoblast ◽  
G Protein Coupled ◽  
Human Trophoblast Cells

AbstractInsufficient invasion of trophoblast cells into the uterine decidua is associated with preeclampsia (PE). G protein-coupled estrogen receptor (GPER) is a membrane estrogen receptor involved in non-genomic estrogen signaling. GPER is expressed in human trophoblast cells and downregulated GPER levels are noted in PE. However, to date, the role of GPER in trophoblast cells remains largely unknown. Here, we applied RNA sequencing (RNA-seq) to HTR-8/SVneo human trophoblast cells in response to G1, an agonist of GPER, and identified angiopoietin-like 4 (ANGPTL4) as a target gene of GPER. Treatment of trophoblast cells with G1 or 17β-estradiol (E2) activated Yes-associated protein (YAP), the major downstream effector of the Hippo pathway, via GPER but in a mammalian STE20-like protein kinase 1 (MST1)-independent manner. Using pharmacological inhibitors as well as loss- and gain-of-function approaches, our results revealed that YAP activation was required for GPER-stimulated ANGPTL4 expression. Transwell invasion assays demonstrated that activation of GPER-induced ANGPTL4 promoted cell invasion. In addition, the expression levels of GPER, YAP, and ANGPTL4 were downregulated in the placenta of patients with PE. Our findings reveal a mechanism by which GPER exerts its stimulatory effect on human trophoblast cell invasion by upregulating YAP-mediated ANGPTL4 expression.

GDF-8 stimulates trophoblast cell invasion by inducing ALK5-SMAD2/3-mediated MMP2 expression

Reproduction ◽  
2021 ◽  
Author(s):  
Lanlan Fang ◽  
Zhen Wang ◽  
Ze Wu ◽  
Yang Yan ◽  
Yibo Gao ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Invasion ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Trophoblast Cell ◽  
Human Trophoblast ◽  
Growth Factor Beta ◽  
Cell Invasiveness ◽  
Extravillous Cytotrophoblast ◽  
Placental Diseases

Matrix metalloproteinases (MMPs) play a pivotal role in the regulation of cell invasion. Placental trophoblast cell invasion is a precisely regulated event. Dysregulation of MMPs has been linked to various placental diseases. Growth differentiation factor-8 (GDF-8), also known as myostatin, is a member of the transforming growth factor-beta (TGF-β) superfamily. GDF-8 and its putative receptors are expressed in human extravillous cytotrophoblast cells (EVTs). Although the pro-invasive effect of GDF-8 in human EVT cells has been recently reported, the underlying molecular mechanism remains largely unknown. In this study, we investigate the effects of GDF-8 on the expression of the two most important MMPs, MMP2 and MMP9, in the HTR-8/SVneo human EVT cell line. Our results show that GDF-8 significantly upregulates the expression of MMP2. The expression of MMP9 is not affected by GDF-8. Using a siRNA-mediated knockdown approach, we reveal that the stimulatory effect of GDF-8 on MMP2 expression is mediated by the ALK5-SMAD2/3 signaling pathway. Additionally, the knockdown of MMP2 attenuates the GDF-8-induced cell invasiveness. These findings deepen our understanding of the biological roles of GDF-8 in the regulation of human trophoblast cell invasion.

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