MicroRNA-590-3p inhibits trophoblast-dependent maternal spiral artery remodeling by repressing low-density lipoprotein receptor-related protein 6.

Abstract

BackgroundThe 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.MethodsHTR‐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.ResultsMiR‐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.ConclusionMicroRNAs‐590‐3p may inhibit trophoblast‐dependent maternal spiral artery remodeling, via both trophoblast invasion and endovascular formation, by repressing LRP6.