ArticleMolecular and cellular biology2012
High-temperature requirement protein A4 (HtrA4) suppresses the fusogenic activity of syncytin-1 and promotes trophoblast invasion.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- Trophoblast-derived proteins and their effects on the pathogenesis of preeclampsia.Histology and histopathology · 2026Review
- Gcm1 Orchestrates Lef1 Expression in Folate Deficiency-Induced Neural Tube Defects.Molecular neurobiology · 2025Article
- Htra4 promotes vascular endothelial cell injury and is associated with the early-onset of preeclampsia.Scientific reports · 2025Article
- Identification of HTRA4 as a Transcriptional Target of p63 in Trophoblast.The American journal of pathology · 2024Article
- Syncytin-1, syncytin-2 and suppressyn in human health and disease.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Article
- The multifaceted role of GCM1 during trophoblast differentiation in the human placenta.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Transcription factor networks in trophoblast development.Cellular and molecular life sciences : CMLS · 2022Review
- Interplay between HTRA1 and classical signalling pathways in organogenesis and diseases.Saudi journal of biological sciences · 2022Review
- Functional antagonism between ΔNp63α and GCM1 regulates human trophoblast stemness and differentiation.Nature communications · 2022Article
- Role of microRNAs in trophoblast invasion and spiral artery remodeling: Implications for preeclampsia.Frontiers in cell and developmental biology · 2022Review
- Overview of Human HtrA Family Proteases and Their Distinctive Physiological Roles and Unique Involvement in Diseases, Especially Cancer and Pregnancy Complications.International journal of molecular sciences · 2021Review
- HtrA4 is up-regulated during trophoblast syncytialization and BeWo cells fail to syncytialize without HtrA4.Scientific reports · 2021Article
- PRG2 and AQPEP are misexpressed in fetal membranes in placenta previa and percreta†.Biology of reproduction · 2021Article
- Transcriptomic Drivers of Differentiation, Maturation, and Polyploidy in Human Extravillous Trophoblast.Frontiers in cell and developmental biology · 2021Article
- Arsenic Trioxide Promotes Tumor Progression by Inducing the Formation of PGCCs and Embryonic Hemoglobin in Colon Cancer Cells.Frontiers in oncology · 2021Article
- Establishment of macaque trophoblast stem cell lines derived from cynomolgus monkey blastocysts.Scientific reports · 2020Article
- HtrA4 may play a major role in inhibiting endothelial repair in pregnancy complication preeclampsia.Scientific reports · 2019Article
- New insights into the regulation of placental growth factor gene expression by the transcription factors GCM1 and DLX3 in human placenta.The Journal of biological chemistry · 2018Article
- DLX3 interacts with GCM1 and inhibits its transactivation-stimulating activity in a homeodomain-dependent manner in human trophoblast-derived cells.Scientific reports · 2017Article
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell-cell fusion and cell invasion are essential for placental development. Human cytotrophoblasts in the chorionic villi may undergo cell-cell fusion to form syncytiotrophoblasts to facilitate nutrient-gas exchange or differentiate into extravillous trophoblasts (EVTs) to facilitate maternal-fetal circulation. The placental transcription factor glial cells missing 1 (GCM1) regulates syncytin-1 and -2 expression to mediate trophoblast fusion. Interestingly, GCM1 and syncytin-1 are also expressed in EVTs with unknown physiological functions. In this study, we performed chromatin immunoprecipitation-on-chip (ChIP-chip) analysis and identified the gene for high-temperature requirement protein A4 (HtrA4) as a GCM1 target gene, which encodes a serine protease facilitating cleavage of fibronectin and invasion of placental cells. Importantly, HtrA4 is immunolocalized in EVTs at the maternal-fetal interface, and its expression is decreased by hypoxia and in preeclampsia, a pregnancy complication associated with placental hypoxia and shallow trophoblast invasion. We further demonstrate that HtrA4 interacts with syncytin-1 and suppresses cell-cell fusion. Therefore, HtrA4 may be crucial for EVT differentiation by playing a dual role in prevention of cell-cell fusion of EVTs and promotion of their invasion into the uterus. Our study reveals a novel function of GCM1 and HtrA4 in regulation of trophoblast invasion and that abnormal HrtA4 expression may contribute to shallow trophoblast invasion in preeclampsia.
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