Reduced SMEK1 regulates trophoblast migration and invasion in fetal growth restriction

IF 3 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta Pub Date : 2025-02-05 DOI:10.1016/j.placenta.2025.02.005

Anna Li , Man Zhao , Ziming Lin , Zexin Yang , Pihai Gong , Chunying Wang , Zhenya Fang , Meihua Zhang

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引用次数: 0

Abstract

Introduction

Fetal growth restriction (FGR) is a significant pregnancy condition characterized by the fetus failing to attain its full genetic growth potential. FGR is primarily ascribed to defective placentation, owing to impaired trophoblast cellular function. The objective of this research is to elucidate the pathogenic functions of suppressor of Mek1 (SMEK1) in FGR.

Methods

Western blot and Immunofluorescence were used to detect the expression and localization of SMEK1 in placenta. We overexpressed and knocked down SMEK1 using plasmid or siRNA special targeted it. EdU Assay, flow cytometry, Western blot, Wound healing migration and Transwell insert assay were used to detect the influence of SMEK1 on cellular function. The mechanism of SMEK1 in regulating the migration of JEG3 cells was predicted by employing transcriptomics and bioinformatics analysis, and was validated by Western blot.

Results

The expression of SMEK1 was downregulated in FGR placentas. The aberrant expression of SMEK1 in JEG3 cells is associated with cell migration and invasion, but not with proliferation, or apoptosis. Transcriptomic analysis and Western blots indicate that knockdown of SMEK1 inhibited the PI3K/Akt/mTOR pathway. A significant inhibition was observed in the epithelial-mesenchymal transition (EMT) process of JEG3 cells within the SMEK1 knockdown group. The activation of the PI3K/Akt/mTOR pathway partially restored the impaired migration and invasive ability due to SMEK1 knockdown in JEG3 cells.

Discussion

the reduction of SMEK1 may contribute to the development of FGR by hindering the EMT process of trophoblast cells through modulation of the PI3K/Akt/mTOR signaling pathway.

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来源期刊

Placenta 医学-发育生物学

CiteScore

6.30

自引率

10.50%

发文量

391

审稿时长

78 days

期刊介绍： Placenta publishes high-quality original articles and invited topical reviews on all aspects of human and animal placentation, and the interactions between the mother, the placenta and fetal development. Topics covered include evolution, development, genetics and epigenetics, stem cells, metabolism, transport, immunology, pathology, pharmacology, cell and molecular biology, and developmental programming. The Editors welcome studies on implantation and the endometrium, comparative placentation, the uterine and umbilical circulations, the relationship between fetal and placental development, clinical aspects of altered placental development or function, the placental membranes, the influence of paternal factors on placental development or function, and the assessment of biomarkers of placental disorders.