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

• Published in: Placenta (Eastbourne) Vol. 118; pp. 55 - 65
• Main Authors: Cao, Chenrui, Dai, Yimin, Wang, Zhiyin, Zhao, Guangfeng, Duan, Honglei, Zhu, Xiangyu, Wang, Jingmei, Zheng, Mingming, Weng, Qiao, Wang, Limin, Gou, Wenjing, Zhang, Haili, Li, Chanjuan, Liu, Dan, Hu, Yali
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.02.2022
• Subjects: Animals; beta Catenin - metabolism; Case-Control Studies; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Differentiation; Cell Movement; Disease Models, Animal; Female; Glycogen Synthase Kinase 3 beta - metabolism; JAM-C; Mice; Mice, Inbred C57BL; Pre-Eclampsia - metabolism; Preeclampsia; Pregnancy; Trophoblast differentiation; Trophoblast invasion; Trophoblasts - physiology; β-catenin; β-catenin; Trophoblast invasion; JAM-C; Preeclampsia; Trophoblast differentiation
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1016/j.placenta.2022.01.003

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. 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. 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. JAM-C plays an important role in normal placentation and upregulated JAM-C in placentas contributes to PE development. •JAM-C is highly expressed on CTBs and downregulated with gestation advance.•JAM-C expression is upregulated in EVTs of with PE patients.•JAM-C restrains trophoblast differentiation, invasion and migration.•JAMC-induced mouse model exhibits a preeclampsia-like phenotype.