子痫前期母胎界面中 CX3CL1/CX3CR1 的高表达抑制滋养细胞侵袭和迁移。
High expression of CX3CL1/CX3CR1 at the mother-fetus interface of preeclampsia inhibits trophoblast invasion and migration.
机构信息
Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China; Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, Shandong, China; Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China; Department of Obstetrics and Gynecology, Liao Cheng People's Hospital, Liaocheng, Shandong, China.
Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
出版信息
Placenta. 2024 Oct;156:30-37. doi: 10.1016/j.placenta.2024.08.008. Epub 2024 Aug 21.
INTRODUCTION
Preeclampsia is associated with maternal inflammatory overreaction and imbalanced immunity at the mother-fetus interface. The pro-inflammatory chemokine fractalkine (CX3CL1) is recently recognized apart from imbalanced immunity. In this study, CX3CL1- CX3C chemokine receptor 1(CX3CR1) regulation of decidual macrophage function and trophoblast invasion ability in preeclampsia was initially explored.
METHODS
The study comprised 60 women allocated to NP group (normotensive pregnant woman, n = 30) and sPE group (woman with severe preeclampsia, n = 30). After the delivery, the expression of CX3CL1 in placental tissues of the two groups was detected by immunohistochemical analysis. The protein level of CX3CL1 in placental tissue and CX3CR1 in decidua tissue was detected by Western Blot and the localization of CX3CR1 expression in decidua was detected by immunofluorescence. Macrophages were polarized into classically activated (M1) macrophages. M1 were treat with PBS (control group), recombinant human CX3CL1 (CX3CL1 group), recombinant human CX3CL1+ selective CX3CR1 antagonist-JMS-17-2 (CX3CL1+anti-CX3CR1 group) and recombinant human CX3CL1 + selective CX3CR1 antagonist-JMS-17-2 + VS-6063 (CX3CL1+anti-CX3CR1+ FAK inhibitor group). M1 and HTR8/SVneo cells were co-cultured as described previously to assess invasion and migration capacity by transwell assays and Wound-healing assay.
RESULTS
In this study, CX3CL1 expression is high in the placental tissues of severe preeclampsia (sPE) patients than in normotensive pregnancies (NP). CX3CR1 expression is high in the decidual tissues of severe preeclampsia patients and mainly expressed in macrophages of decidual tissues. CX3CL1/CX3CR1 decreased VEGF expression in M1 macrophages and reduced the invasion and migration function of HTR-8/SVneo through the FAK signaling pathway.
DISCUSSION
These findings revealed that CX3CL1-CX3CR1 regulate the trophoblast function by FAK and provided new insights into the pathogenesis of preeclampsia.
简介
子痫前期与母体炎症过度反应和母胎界面免疫失衡有关。趋化因子 fractalkine（CX3CL1）除了免疫失衡外，最近也被认为与子痫前期有关。本研究初步探讨了 CX3CL1-CX3C 趋化因子受体 1（CX3CR1）对蜕膜巨噬细胞功能和滋养细胞侵袭能力的调节作用。
方法
本研究纳入了 60 名女性，分为 NP 组（正常血压孕妇，n=30）和 sPE 组（严重子痫前期患者，n=30）。分娩后，通过免疫组化分析检测两组胎盘组织中 CX3CL1 的表达。通过 Western Blot 检测胎盘组织中 CX3CL1 的蛋白水平和蜕膜组织中 CX3CR1 的蛋白水平，并通过免疫荧光检测 CX3CR1 在蜕膜中的表达定位。将巨噬细胞极化诱导为经典激活型（M1）巨噬细胞。将 M1 分别用 PBS（对照组）、重组人 CX3CL1（CX3CL1 组）、重组人 CX3CL1+选择性 CX3CR1 拮抗剂 JMS-17-2（CX3CL1+anti-CX3CR1 组）和重组人 CX3CL1+选择性 CX3CR1 拮抗剂 JMS-17-2+VS-6063（CX3CL1+anti-CX3CR1+FAK 抑制剂组）处理。如前所述，将 M1 和 HTR8/SVneo 细胞共培养，通过 Transwell 实验和划痕实验评估侵袭和迁移能力。
结果
本研究中，严重子痫前期（sPE）患者胎盘组织中 CX3CL1 的表达高于正常血压妊娠（NP）患者。CX3CR1 在严重子痫前期患者的蜕膜组织中高表达，主要表达在蜕膜组织中的巨噬细胞上。CX3CL1/CX3CR1 通过 FAK 信号通路降低 M1 巨噬细胞中 VEGF 的表达，并降低 HTR-8/SVneo 的侵袭和迁移功能。
讨论
这些发现表明，CX3CL1-CX3CR1 通过 FAK 调节滋养细胞功能，为子痫前期的发病机制提供了新的见解。
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