ACVR2A facilitates trophoblast cell invasion through TCF7/c-JUN pathway in pre-eclampsia progression

Pre-eclampsia (PE) is a serious pregnancy disorder linked to genetic factors, particularly the ACVR2A gene, which encodes a receptor involved in the activin signaling pathway and plays a critical role in reproductive processes. Transcriptomic data analysis and experimental verification confirmed a d...

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Main Authors: Shujing Yang, Huanyao Liu, Jieshi Hu, Binjun Chen, Wanlu An, Xuwen Song, Yi Yang, Fang He
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2025-05-01
Series:eLife
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Online Access:https://elifesciences.org/articles/101236
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Summary:Pre-eclampsia (PE) is a serious pregnancy disorder linked to genetic factors, particularly the ACVR2A gene, which encodes a receptor involved in the activin signaling pathway and plays a critical role in reproductive processes. Transcriptomic data analysis and experimental verification confirmed a downregulation of ACVR2A expression in placental tissues from PE patients. In this study, CRISPR/Cas9 technology was employed to investigate the effect of ACVR2A gene deletion on trophoblast cells using the HTR8/SVneo and JAR cell lines. Deletion of ACVR2A inhibits trophoblastic migration, proliferation, and invasion, underscoring its pivotal role in cellular function. RNA-seq data analysis unveiled an intricate regulatory network influenced by ACVR2A gene knockout, especially in the TCF7/c-JUN pathway. By employing RT-PCR and immunohistochemical analysis, a potential association between ACVR2A and the TCF7/c-JUN pathway was hypothesized and confirmed. The complexity of PE onset and the significance of genetic factors were emphasized, particularly the role of the ACVR2A gene identified in genome-wide association study. This study established a robust foundation for delving deeper into the intricate mechanisms of PE, paving the way for focused early intervention, personalized treatment, and enhanced obstetric healthcare.
ISSN:2050-084X