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.

scholarly journals Dual effect of transforming growth factor β1 on cell adhesion and invasion in human placenta trophoblast cells

Reproduction ◽  
2006 ◽  
Vol 132 (2) ◽  
pp. 333-341 ◽  
Author(s):  
Mei-rong Zhao ◽  
Wei Qiu ◽  
Yu-xia Li ◽  
Zhi-bin Zhang ◽  
Dong Li ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Growth Factor ◽  
Mrna Expression ◽  
Cell Invasion ◽  
Human Placenta ◽  
Transforming Growth Factor ◽  
Trophoblast Cell ◽  
Rt Pcr ◽  
Human Trophoblast ◽  
Adhesion And Invasion

Transforming growth factor β (TGFβ) has been shown to be a multifunctional cytokine required for embryonic development and regulation of trophoblast cell behaviors. In the present study, a non-transformed cell-line representative of normal human trophoblast (NPC) was used to examine the effect of TGFβ1 on trophoblast cell adhesion and invasion. In vitro assay showed that TGFβ1 could significantly promote intercellular adhesion, while inhibiting cell invasion across the collagen I-coated filter. Reverse transcription (RT)-PCR and gelatin zymography demonstrated that TGFβ1 evidently repressed the mRNA expression and proenzyme production of matrix metalloproteinase (MMP)-9, but exerted no effect on mRNA expression and secretion of MMP-2. On the other hand, both the mRNA and protein expression of epithelial-cadherin and β-catenin were obviously upregulated by TGFβ1 in dose-dependent fashion, as revealed by RT-PCR and western-blot analysis. What is more, one of the critical TGFβ signaling molecules – Smad2 was notably phosphorylated in TGFβ1-treated NPC cells. The data indicates that cell invasion and adhesion are coordinated processes in human trophoblasts and that there exists paracrine regulation on adhesion molecules and invasion-associated enzymes in human placenta.

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