ArticlePloS one2013
Trophoblast cell fusion and differentiation are mediated by both the protein kinase C and a pathways.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 52 citations in OpenAlex.
- Article
- Trophoblast Fusion Deficiency in Placenta-Related Pregnancy Disorders.Advances in experimental medicine and biology · 2026Review
- Understanding the involvement of HtrA4 during syncytiotrophoblast differentiation.Frontiers in cell and developmental biology · 2026Article
- The multifactorial role of HDAC9 at the maternal-fetal interface in the pathogenesis of preeclampsia.Clinical science (London, England : 1979) · 2025Review
- Manifold roles of the chemokine G-protein-coupled receptor CCR7 in differentiation of human trophoblast into extravillous and syncytiotrophoblast lineages.Development (Cambridge, England) · 2025Article
- Epidermal growth factor receptor in placental health and disease: pathways, dysfunction, and chemical disruption.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- Downregulation of SPARC Expression Enhances the Fusion of BeWo Choriocarcinoma Cells.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- Establishment and comparison of human term placenta-derived trophoblast cells†.Biology of reproduction · 2024Article
- Lipid nanoparticle structure and delivery route during pregnancy dictate mRNA potency, immunogenicity, and maternal and fetal outcomes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Mitochondrial citrate metabolism and efflux regulate BeWo differentiation.Scientific reports · 2023Article
- Ancestry dependent balancing selection of placental dysferlin at high-altitude.Frontiers in cell and developmental biology · 2023Article
- Metformin impairs trophoblast metabolism and differentiation in a dose-dependent manner.Frontiers in cell and developmental biology · 2023Article
- How trophoblasts fuse: an in-depth look into placental syncytiotrophoblast formation.Cellular and molecular life sciences : CMLS · 2022Review
- Inefficient development of syncytiotrophoblasts in theProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Cell-Cell Fusion Mediated by Viruses and HERV-Derived Fusogens in Cancer Initiation and Progression.Cancers · 2021Review
- HtrA4 is up-regulated during trophoblast syncytialization and BeWo cells fail to syncytialize without HtrA4.Scientific reports · 2021Article
- Human Placental Trophoblasts Infected byFrontiers in immunology · 2021Article
- RNA-Seq identifies genes whose proteins are upregulated during syncytia development in murine C2C12 myoblasts and human BeWo trophoblasts.Physiological reports · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The syncytiotrophoblast of the human placenta is an epithelial barrier that interacts with maternal blood and is a key for the transfer of nutrients and other solutes to the developing fetus. The syncytiotrophoblast is a true syncytium and fusion of progenitor cytotrophoblasts is the cardinal event leading to the formation of this layer. BeWo cells are often used as a surrogate for cytotrophoblasts, since they can be induced to fuse, and then express certain differentiation markers associated with trophoblast syncytialization. Dysferlin, a syncytiotrophoblast membrane repair protein, is up-regulated in BeWo cells induced to fuse by treatment with forskolin; this fusion is thought to occur through cAMP/protein kinase A-dependent mechanisms. We hypothesized that dysferlin may also be up-regulated in response to fusion through other pathways. Here, we show that BeWo cells can also be induced to fuse by treatment with an activator of protein kinase C, and that this fusion is accompanied by increased expression of dysferlin. Moreover, a dramatic synergistic increase in dysferlin expression is observed when both the protein kinase A and protein kinase C pathways are activated in BeWo cells. This synergy in fusion is also accompanied by dramatic increases in mRNA for the placental fusion proteins syncytin 1, syncytin 2, as well as dysferlin. Dysferlin, however, was shown to be dispensable for stimulus-induced BeWo cell syncytialization, since dysferlin knockdown lines fused to the same extent as control cells. The classical trophoblast differentiation marker human chorionic gonadotropin was also monitored and changes in the expression closely parallel that of dysferlin in all of the experimental conditions employed. Thus different biochemical markers of trophoblast fusion behave in concert supporting the hypothesis that activation of both protein kinase C and A pathways lead to trophoblastic differentiation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.