2. Academic Validation
  3. 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.
PMID: 35032792 DOI: 10.1016/j.placenta.2022.01.003
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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