Snail mediates GDF-8-stimulated human extravillous trophoblast cell invasion by upregulating MMP2 expression

• Published in: Cell communication and signaling 2023-05, Vol.21 (1), p.93-93, Article 93
• Main Authors: Chen, Jiaye, Song, Tinglin, Yang, Sizhu, Meng, Qingxue, Han, Xiaoyu, Wu, Ze, Cheng, Jung-Chien, Fang, Lanlan
• Format: Article
• Language: English
• Subjects: Antibodies; Antigens; Cancer; Cell adhesion & migration; Cell culture; Cell differentiation; Cell Movement; Female; GDF-8; Gelatinase A; Gene silencing; Growth factors; Humans; Invasion; Invasiveness; Laboratories; Matrix metalloproteinase; Matrix Metalloproteinase 2 - metabolism; Membranes; Metalloproteinase; MMP2; Molecular modelling; Myostatin - metabolism; Myostatin - pharmacology; Penicillin; Placenta; Pre-eclampsia; Pregnancy; Pregnancy complications; RNA, Small Interfering - metabolism; siRNA; Smad4 protein; Snail; Transforming Growth Factor beta - metabolism; Transforming growth factor-b; Trophoblast cells; Trophoblasts - metabolism
• ISSN: 1478-811X; 1478-811X
• DOI: 10.1186/s12964-023-01107-2

Extravillous trophoblast (EVT) cell invasion is a tightly regulated process that requires for a normal pregnancy. The epithelial-mesenchymal transition (EMT) has been implicated in EVT cell invasion. Growth differentiation factor-8 (GDF-8), a member of the transforming growth factor-beta (TGF-β) superfamily, is expressed in the human placenta and promotes EVT cell invasion by upregulating the expression of matrix metalloproteinase 2 (MMP2). However, the underlying molecular mechanism of GDF-8-induced MMP2 expression remains undetermined. Therefore, the present study aims to examine the role of Snail and Slug, the EMT-related transcriptional regulators, in GDF-8-stimulated MMP2 expression and cell invasion in HTR-8/SVneo human EVT cell line and primary cultures of human EVT cells. HTR-8/SVneo and primary cultures of human EVT cells were used to examine the effect of GDF-8 on MMP2 expression and explore the underlying mechanism. For gene silencing and overexpression, the HTR-8/SVneo cell line was used to make the experiments more technically feasible. The cell invasiveness was measured by Matrigel-coated transwell invasion assay. GDF-8 stimulated MMP2 expression in both HTR-8/SVneo and primary EVT cells. The stimulatory effect of GDF-8 on MMP2 expression was blocked by the inhibitor of TGF-β type-I receptors, SB431542. Treatment with GDF-8 upregulated Snail and Slug expression in both HTR-8/SVneo and primary EVT cells. The stimulatory effects of GDF-8 on Snail and Slug expression were blocked by pretreatment of SB431542 and siRNA-mediated knockdown of SMAD4. Interestingly, using the siRNA knockdown approach, our results showed that Snail but not Slug was required for the GDF-8-induced MMP2 expression and cell invasion in HTR-8/SVneo cells. The reduction of MMP2 expression in the placentas with preeclampsia (PE) was also observed. These findings discover the physiological function of GDF-8 in the human placenta and provide important insights into the regulation of MMP2 expression in human EVT cells. Video Abstract.