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

Abstract

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.

• Authors: Lanlan Fang, Zhen Wang, Ze Wu, Yang Yan, Yibo Gao, Yuxi Li, Jung-Chien Cheng, Ying-Pu Sun
• Journal: Reproduction (Cambridge, England) (Reproduction) Vol. 162 Issue 5 Pg. 331-338 (10 05 2021) ISSN: 1741-7899 [Electronic] England
• PMID: 34432647 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MSTN protein, human
• Myostatin
• SMAD2 protein, human
• SMAD3 protein, human
• Smad2 Protein
• Smad3 Protein
• Transforming Growth Factor beta
• Receptor, Transforming Growth Factor-beta Type I
• TGFBR1 protein, human
• MMP2 protein, human
• Matrix Metalloproteinase 2

Topics

• Cell Movement
• Female
• Humans
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Myostatin (metabolism)
• Placenta (metabolism)
• Pregnancy
• Receptor, Transforming Growth Factor-beta Type I
• Smad2 Protein (metabolism)
• Smad3 Protein
• Transforming Growth Factor beta (metabolism)
• Trophoblasts (metabolism)