ArticleReproductive biology and endocrinology : RB&E2021
Alpha-actinin-4 is essential for maintaining normal trophoblast proliferation and differentiation during early pregnancy.
Article in Reproductive biology and endocrinology : RB&E, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 17 citations in OpenAlex.
- Protein networks are influenced by maternal BMI and differentiate preterm birth types.Communications medicine · 2026Article
- Exploring the potential role of palladin in modulating human CAF/ECM functional units.Cytoskeleton (Hoboken, N.J.) · 2025Review
- Associations Between Prenatal Vitamin D and Placental Gene Expression.The Journal of nutrition · 2024Article
- Associations Between Prenatal Vitamin D and Placental Gene Expression.bioRxiv : the preprint server for biology · 2024Article
- Exosome-delivered miR-410-3p reverses epithelial-mesenchymal transition, migration and invasion of trophoblasts in spontaneous abortion.Journal of cellular and molecular medicine · 2024Article
- Placental proteome in late‑onset of fetal growth restriction.Molecular medicine reports · 2022Article
- Bioinformatics analysis identification ofExperimental and therapeutic medicine · 2022Article
- Systematic proteomics analysis of lysine acetylation reveals critical features of placental proteins in pregnant women with preeclampsia.Journal of cellular and molecular medicine · 2021Article
- Altered protein O-GlcNAcylation in placentas from mothers with diabetes causes aberrant endocytosis in placental trophoblast cells.Scientific reports · 2021Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundProper differentiation of trophoblasts in the human placenta is essential for a successful pregnancy, whereas abnormal regulation of this process may lead to adverse pregnancy outcomes, especially preeclampsia (PE). However, the underlying mechanism of trophoblast differentiation remains unclear. Previous studies have reported the involvement of alpha-actinin-4 (ACTN4) in the actin cytoskeleton dynamics and motility. Hence, we hypothesized that ACTN4 may act as an important regulator in the normal proliferation and differentiation of trophoblasts during early pregnancy.
methodTo test this hypothesis, we collected villous tissues from women undergoing a legal pregnancy termination during 6-10 weeks of gestation and explanted them for cell culture and siRNA transfection. We also obtained placental tissues from PE patients and healthy pregnant women and isolated the primary cytotrophoblast (CTB) cells. The expression of ACTN4 in the CTBs of placental villi and during the differentiation of CTBs into STBs was detected by immunofluorescence, immunohistochemistry (IHC), and EdU proliferation assays. Besides, villous explant, Matrigel invasion, transwell migration assay, and Wound-healing assay were performed to identify the possible role of ACTN4 in the outgrowth of explants and the invasion, migration, and proliferation of cell column trophoblasts (CCTs). Western blot analysis was carried out to compare the protein expression level of AKT, Snail activities, and epithelial-to-mesenchymal transition (EMT) in the villi or HTR8/SVneo cells with ACTN4 knockdown.
resultsACTN4 was highly expressed in CTB cells and interstitial extravillous trophoblast (iEVT) cells but not found in the syncytiotrophoblast (STB) cells in the first trimester villi. Downregulation of ACTN4 led to reduced trophoblast proliferation and explant outgrowth ex vivo, as well as iEVT invasion and migration in vitro due to disrupt of actin filaments organization. Such ACTN4 inhibition also decreased AKT and Snail activities and further impeded the EMT process. In addition, ACTN4 expression was found to be downregulated in the iEVTs from preeclamptic placentas.
conclusionsOur findings suggest that ACTN4 may act as an important regulator of trophoblast proliferation and differentiation during early pregnancy, and dysregulation of this protein may contribute to preeclampsia pathogenesis.
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