Galectin-14 Promotes Trophoblast Migration and Invasion by Upregulating the Expression of MMP-9 and N-Cadherin

Abstract

Galectin-14 is specifically expressed in placental trophoblasts, and its expression is reduced in trophoblasts retrieved from the cervix of women destined to develop early pregnancy loss. However, the roles of galectin-14 in regulating trophoblasts and in the pathogenesis of pregnancy complication have never been investigated. In the current research, we aimed to investigate the roles of galectin-14 in the regulation of trophoblasts. Tissues of the placenta and villi were collected. Primary trophoblasts and human trophoblast cell line HTR-8/SVneo were used. Western blotting and RT-PCR were used to quantify gene expression. The siRNA-mediated galectin-14 knockdown and lentivirus-mediated overexpression were performed to manipulate the gene expression in trophoblasts. Transwell migration and invasion assays were used to evaluate cell migration and invasion capacity. Gelatin zymography was used to determine the gelatinase activity. Galectin-14 was significantly decreased in the villi of early pregnancy loss and the placenta of preeclampsia. Knockdown of galectin-14 in primary trophoblasts inhibited cell migration and invasion, downregulated the expression of matrix metalloproteinase (MMP)-9 and N-cadherin, the activity of MMP-9, and decreased the phosphorylation of Akt. Meanwhile, the overexpression of galectin-14 in HTR-8/SVneo promoted cell migration and invasion, upregulated the expression of MMP-9 and N-cadherin, the activity of MMP-9, and increased the phosphorylation of Akt. Increased Akt phosphorylation promoted cell migration and invasion and upregulated the expression and activity of MMP-9, while decreased Akt phosphorylation inhibited cell migration and invasion and downregulated the expression and activity of MMP-9. Thus, galectin-14 promotes trophoblast migration and invasion by enhancing the expression of MMP-9 and N-cadherin through Akt phosphorylation. The dysregulation of galectin-14 is involved in the pathogenesis of early pregnancy loss and preeclampsia.

Krüppel‐like factor 6 participates in extravillous trophoblast cell differentiation and its expression is reduced in abnormally invasive placenta

“…Enhanced Cx43 level is also correlated with the promotion of cell migration in tumor contexts [59–61]. N‐cadherin is not only one of the hallmarks of the EMT switch in tumorigenesis and metastasis [62], but its role in promoting primary trophoblast and HTR‐8/SVneo cell migration [63] and invasion [64] has also been demonstrated. The importance of MMP9 in trophoblastic cell migration and invasion, and its dysregulation in complicated pregnancies, has been the subject of intense research.…”

Transcriptomic mapping of the metzincin landscape in human trophoblasts

“…Absent from this list is MMP9, a matrix metalloprotease often described as an EVT marker important in controlling trophoblast invasion [55]. It should be noted that the majority of (if not all) studies describing MMP9 expression specificity to invasive trophoblast subsets characterized and tested MMP9 function in immortalized trophoblastic cell lines [56] or inadequately described primary trophoblast cultures [57]. This latter example is especially important as primary cultures of CTB and EVT are challenging to establish and experiment on.…”

Possible important roles of galectins in the healing of human fetal membranes

“…Microarray analysis showed that treatment with galectin-1 induced upregulation of genes encoding matrix metalloproteinases MMP-1, MMP-10, MMP-12 and tissue fibrinogen activator in dendritic cells, which was associated with increased migratory activity of these antigen-presenting cells ( 71 ). In addition, transfection of galectin-4cDNA into placental trophoblast cells induced enhanced Akt phosphorylation upregulated the expression of MMP-9 and N-Cadherin, promoting trophoblast migration and invasion ( 72 ).…”