1. Academic Validation
  2. The role of junctional adhesion molecule-C in trophoblast differentiation and function during normal pregnancy and preeclampsia

The role of junctional adhesion molecule-C in trophoblast differentiation and function during normal pregnancy and preeclampsia

  • Placenta. 2022 Feb;118:55-65. doi: 10.1016/j.placenta.2022.01.003.
Chenrui Cao 1 Yimin Dai 1 Zhiyin Wang 1 Guangfeng Zhao 1 Honglei Duan 1 Xiangyu Zhu 1 Jingmei Wang 2 Mingming Zheng 1 Qiao Weng 1 Limin Wang 1 Wenjing Gou 1 Haili Zhang 3 Chanjuan Li 4 Dan Liu 5 Yali Hu 6
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
  • 2 Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
  • 3 Department of Obstetrics and Gynecology, The First People's Hospital of Mangya, Qinghai, China.
  • 4 Department of Obstetrics, Women's Hospital of Nanjing Medical University, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Heath Care Hospital, Nanjing, China.
  • 5 Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China. Electronic address: liudan870718@126.com.
  • 6 Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China. Electronic address: yalihu@nju.edu.cn.
Abstract

Introduction: Junctional adhesion molecule-C (JAM-C) is an important regulator of many physiological processes, ranging from maintenance of tight junction integrity of epithelia to regulation of cell migration, homing and proliferation. Preeclampsia (PE) is a trophoblast-related syndrome with abnormal placentation and insufficient trophoblast invasion. However, the role of JAM-C in normal pregnancy and PE pathogenesis is unknown.

Methods: The expression and location of JAM-C in placentas were determined by quantitative Real-Time PCR (qRT-PCR), western blot and immunohistochemistry. The expression of differentiation and invasion markers were detected by qRT-PCR or western blot. The effects of JAM-C on migration and invasion of trophoblasts were examined using wound-healing and invasion assays. Additionally, a mouse model was established by injection of JAM-C-positive adenovirus to explore the effects of JAM-C in vivo.

Results: In normal pregnancy, JAM-C was preferentially expressed on cytotrophoblast (CTB) progenitors and progressively decreased when acquiring invasion properties with gestation advance. However, in PE patients, the expression of JAM-C was upregulated in extravillous trophoblasts (EVTs) and syncytiotrophoblasts (SynTs) of placentas. It was also demonstrated that JAM-C suppressed the differentiation of CTBs into EVTs in vitro. Consistently, JAM-C inhibited the migration and invasion capacities of EVTs through GSK3β/β-catenin signaling pathway. Importantly, Ad-JAMC-infected mouse model mimicked the phenotype of human PE.

Discussion: JAM-C plays an important role in normal placentation and upregulated JAM-C in placentas contributes to PE development.

Keywords

JAM-C; Preeclampsia; Trophoblast differentiation; Trophoblast invasion; β-catenin.

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