BACKGROUND Integrins are transmembrane receptors that mediate cell-extracellular matrix (ECM) and cell-cell adhesion and trophoblast cells undergo changes in integrin expression as they differentiate. However, the mechanism(s) of integrin activation leading to integrin-mediated signaling in trophoblast cell differentiation is unknown. The Fermitin family proteins are integrin activators that help mediate integrin-mediated signaling, but have never been studied in detail within the human placenta. Thus, we examined the spatiotemporal pattern of expression of Fermitin family homolog-2 (FERMT2) in human chorionic villi throughout gestation and its role in trophoblast-substrate adhesion and invasion. METHODS Placental villous tissue was obtained from patients undergoing elective terminations by dilatation and curettage at weeks 8-12 (n = 10), weeks 13-14 (n = 8), as well as from term deliveries at weeks 37-40 (n = 6). Tissues were fixed, processed and sections utilized for immunofluorescence analysis of FERMT2 expression during gestation. Additionally, HTR8-SVneo human trophoblast cells were transfected by electroporation with FERMT2-specific siRNAs or non-targeting siRNAs (control) and used in cell-substrate adhesion as well as invasion assays. RESULTS FERMT2 was more commonly expressed in the basal domain of villous cytotrophoblast cells and prominently localized around the periphery of individual extravillous trophoblast cells. siRNA-mediated knockdown of FERMT2 in HTR8-SVneo cells resulted in significantly decreased trophoblast-substrate attachment (p < 0.05) as well as significantly decreased trophoblast invasion (p < 0.05) relative to control cells. CONCLUSIONS The detection of FERMT2 throughout extravillous trophoblast columns and the results of invasion assays demonstrated that this protein is likely an important regulator of integrin activation in extravillous cells to modulate migration and invasion.

中文翻译：

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Fermitin家族同系物2（FERMT2）在人类胎盘绒毛中高度表达，并调节滋养细胞的侵袭。

背景技术整联蛋白是介导细胞-细胞外基质（ECM）和细胞-细胞粘附和滋养层细胞随着它们分化而经历整联蛋白表达变化的跨膜受体。然而，在滋养层细胞分化中导致整合素介导的信号传导的整合素活化的机制尚不清楚。Fermitin家族蛋白是整合素激活剂，可帮助介导整合素介导的信号传导，但从未在人类胎盘中进行过详细研究。因此，我们检查了整个妊娠过程中人绒毛膜绒毛中Fermitin家族同源物2（FERMT2）表达的时空模式及其在滋养层基质粘附和侵袭中的作用。方法胎盘绒毛组织取自于第8-12周（n = 10）通过刮宫和刮宫术进行选择性终止的患者，第13-14周（n = 8），以及第37-40周的足月分娩（n = 6）。固定，处理组织并将切片用于妊娠期FERMT2表达的免疫荧光分析。此外，HTR8-SVneo人滋养层细胞通过用FERMT2特异性siRNA或非靶向siRNA（对照）进行电穿孔转染，并用于细胞-基质粘附以及侵袭试验。结果FERMT2在绒毛滋养层细胞的基底结构域中更普遍表达，并显着分布在单个绒毛外滋养层细胞的周围。相对于对照细胞，siRNA介导的HTR8-SVneo细胞中FERMT2的敲低显着降低了滋养层-底物附着（p <0.05），并显着降低了滋养层侵袭（p <0.05）。