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. 2025 Aug:168:56-66.
doi: 10.1016/j.placenta.2025.06.011. Epub 2025 Jun 11.

Insufficient expression of VTN promotes the development of early-onset severe preeclampsia through the HEY1/autophagy signaling pathway

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Insufficient expression of VTN promotes the development of early-onset severe preeclampsia through the HEY1/autophagy signaling pathway

Gonghua Qi et al. Placenta. 2025 Aug.

Abstract

Introduction: Early-onset severe preeclampsia (eosPE) is a serious pregnancy complication that affects maternal and fetal health. This study aims to identify genes involved in the development of eosPE by analyzing placental tissues from eosPE patients and healthy controls.

Methods: We performed Gene Ontology (GO) analysis on differentially expressed genes (DEGs) from the placental tissues of eosPE patients and healthy controls using data from the GEO database. Vitronectin (VTN), a gene identified as relevant in the top three molecular function categories, was further investigated. Functional assays were conducted on HTR8/SVneo cells, HUVECs, and primary extravillous trophoblasts (EVTs). Additionally, transcriptome sequencing was performed to study the impact of VTN overexpression on signaling pathways.

Results: VTN was found to be significantly downregulated in eosPE placental tissues compared to healthy controls. Functional assays demonstrated that VTN enhanced migration, invasion, and tube formation in trophoblast cells. VTN overexpression impacted the Notch signaling pathway, upregulating HEY1, a downstream target. HEY1 was also found to be downregulated in eosPE placental tissues. Knockdown of VTN led to increased LC3II expression, indicating enhanced autophagy, while HEY1 overexpression alleviated this effect. Autophagy inhibition with 3-MA partially restored function suppressed by VTN knockdown.

Discussion: Our findings suggest that insufficient VTN expression impairs trophoblast cell migration, invasion, and endothelial-like tube formation through the HEY1/autophagy pathway, contributing to eosPE pathogenesis. This highlights VTN's potential role in the development of eosPE and suggests new therapeutic targets for managing this pregnancy complication.

Keywords: Autophagy; Early-onset severe preeclampsia (eosPE); HEY1; VTN.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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