Transmembrane integrin receptors mediate cell–extracellular matrix as well as cell–cell adhesion. As placental trophoblast cells undergo differentiation they display changes in integrin expression or switching, but the mechanism(s) of integrin activation that supports this differentiation is still unknown. The Fermitin family of adapter proteins (FERMT 1–3) are integrin activators that mediate integrin-mediated signaling. In this study, we examined the spatiotemporal pattern of expression of FERMT1 in human chorionic villi throughout gestation and its role in HTR8-SVneo substrate adhesion and invasion. Placental villous tissue was obtained from patients undergoing elective terminations at weeks 8–14, as well as from term deliveries at weeks 37–40 and analyzed by immunofluorescence. Additionally, HTR8-SVneo trophoblast cells were transfected with FERMT1-specific siRNA or non-targeting siRNA (control) and used in cell-substrate adhesion as well as invasion assays. FERMT1 was primarily localized to membrane-associated regions at the base or around the periphery of the villous cytotrophoblast and proximal as well as distal cell column trophoblast. FERMT1 was also localized to endothelial cells of blood vessels in chorionic villi. siRNA-mediated depletion of FERMT1 in HTR8-SVneo cells did not markedly alter HTR8-SVneo cell-substrate adhesion but did significantly decrease invasion (P < 0.05) compared to control cells. These novel findings identify the presence of the integrin activator FERMT1 in trophoblast cells and that FERMT1 can regulate HTR8-SVneo cell invasion. FERMT1 may directly influence integrin activation and the subsequent integrin-mediated signaling and differentiation that underlies the acquisition of the invasive trophoblast phenotype in vivo.

跨膜整合素受体介导细胞-细胞外基质以及细胞-细胞粘附。随着胎盘滋养层细胞经历分化，它们显示出整合素表达或转换的变化，但支持这种分化的整合素激活机制仍然未知。Fermitin 衔接蛋白家族 (FERMT 1–3) 是整合素激活剂，可介导整合素介导的信号传导。在这项研究中，我们检查了整个妊娠期间人绒毛膜绒毛中 FERMT1 表达的时空模式及其在 HTR8-SVneo 底物粘附和侵袭中的作用。胎盘绒毛组织取自在第 8-14 周进行选择性终止妊娠的患者以及第 37-40 周的足月分娩，并通过免疫荧光进行分析。此外，HTR8-SVneo 滋养层细胞用 FERMT1 特异性 siRNA 或非靶向 siRNA（对照）转染，并用于细胞-底物粘附和侵袭测定。FERMT1 主要位于绒毛细胞滋养层和近端以及远端细胞柱滋养层底部或周围的膜相关区域。FERMT1 也定位于绒毛膜绒毛血管的内皮细胞。在 HTR8-SVneo 细胞中，siRNA 介导的 FERMT1 消耗没有显着改变 HTR8-SVneo 细胞 - 底物粘附，但确实显着降低了侵袭。FERMT1 主要位于绒毛细胞滋养层和近端以及远端细胞柱滋养层底部或周围的膜相关区域。FERMT1 也定位于绒毛膜绒毛血管的内皮细胞。在 HTR8-SVneo 细胞中，siRNA 介导的 FERMT1 消耗没有显着改变 HTR8-SVneo 细胞 - 底物粘附，但确实显着降低了侵袭。FERMT1 主要位于绒毛细胞滋养层和近端以及远端细胞柱滋养层底部或周围的膜相关区域。FERMT1 也定位于绒毛膜绒毛血管的内皮细胞。在 HTR8-SVneo 细胞中，siRNA 介导的 FERMT1 消耗没有显着改变 HTR8-SVneo 细胞 - 底物粘附，但确实显着降低了侵袭。P  < 0.05) 与对照细胞相比。这些新发现确定了滋养层细胞中整合素激活剂 FERMT1 的存在，并且 FERMT1 可以调节 HTR8-SVneo 细胞侵袭。FERMT1 可能直接影响整合素激活和随后的整合素介导的信号传导和分化，这是体内侵袭性滋养细胞表型获得的基础。