Background
The remodeling of maternal spiral artery following embryo implantation, which relies on well-regulated trophoblast functions, is a pivotal process to ensure a successful pregnancy. Low-density lipoprotein receptor-related protein 6 (LRP6) and microRNAs (miRNAs, miRs) are suggested to be involved in angiogenesis and several vascular diseases; however, their functions in the control of trophoblast remain elusive. We therefore aimed to examine the roles of LRP6 and miR-590-3p in the regulation of trophoblast during the remodeling of maternal spiral artery.
Conclusion
MicroRNAs-590-3p may inhibit trophoblast-dependent maternal spiral artery remodeling, via both trophoblast invasion and endovascular formation, by repressing LRP6.
Methods
HTR-8/SVneo cell, a trophoblast cell line, was utilized to study the effects of LRP6 and miR-590-3p on apoptosis, cell proliferation, migration, invasion, as well as tube formation. Expression of angiogenic factors placental growth factor (PlGF), matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and activities of canonical Wnt/β-catenin signaling pathway, which were implicated in the process of artery remodeling, were also examined.
Results
MiR-590-3p directly targeted 3' untranslated region (3'-UTR) of LRP6 mRNA and repressed LRP6 expression, which in turn inhibited proliferation, migration, invasion, as well as tube formation, and resulted in apoptosis in HTR-8/SVneo cells. Further, inhibition of LRP6 through miR-590-3p significantly suppressed the expression of PlGF, MMPs, and VEGF and reduced the activation of Wnt/β-catenin signaling pathway.