2. Academic Validation
  3. High expression of CX3CL1/CX3CR1 at the mother-fetus interface of preeclampsia inhibits trophoblast invasion and migration

High expression of CX3CL1/CX3CR1 at the mother-fetus interface of preeclampsia inhibits trophoblast invasion and migration

  • Placenta. 2024 Aug 21:156:30-37. doi: 10.1016/j.placenta.2024.08.008.
Haixia Liu 1,  Ping Wang 2,  Junbin Yin 3,  Ping Yang 2,  Jingjing Shi 2,  Aihua Li 4,  Xietong Wang 5,  Jinlai Meng 6
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
  • 3 Department of Neurology, The 960th Hospital of PLA, Jinan, Shandong, China.
  • 4 Department of Obstetrics and Gynecology, Liao Cheng People's Hospital, Liaocheng, Shandong, China.
  • 5 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.
  • 6 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. Electronic address: mengjinlai2024@163.com.
PMID: 39236525 DOI: 10.1016/j.placenta.2024.08.008
Abstract

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.

Keywords

CX3CR1; FAK; Fractalkine/CX3CL1; Macrophage; Preeclampsia; Pregnancy; VEGF.

Figures
Products
Inhibitors & Agonists
Other Products