FAK regulates trophoblast functions of invasion and proliferation through Rap1 pathway in preeclampsia
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PROVIDER: PRJNA1134162 | ENA |
REPOSITORIES: ENA
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Project description:To explore the potential role of focal adhesion kinase (FAK) in trophoblast functions in early-onset preeclampsia (EOPE).We first examined expression and localization in placental tissue as well as in villus tissue during early pregnancy. Then, FAK activity was inhibited with Y15. The effects of FAK on the invasion and proliferation of trophoblast cells (HTR8/SVneo) were investigated. Transcriptomic and bioinformatics analyses were then used to predict the possible pathways by which FAK is involved in PE. Finally, we measured the expression of FAK in a PE mouse model. Transcriptomic and bioinformatics results suggest that Rap1 may be a downstream regulator of trophoblast FAK. In mouse models, we found reduced expression of FAK and Rap1 in the placenta of PE mice.
2025-07-10 | GSE271940 | GEO
Project description:Placentation requires the proper regulation of extravillous trophoblast (EVT) migration and invasion into the decidua and maternal vasculature, processes which are initiated in physiologic hypoxic conditions. Abnormal EVT migration and/or invasion have been suggested to lead to pregnancy complications, such as preeclampsia. The objectives of this study are to determine how exposure to hypoxia impacts gene expression and cellular motility of first trimester trophoblasts, and to assess if expression of migration-associated genes is dysregulated in 2nd trimester chorionic villous samples (CVS) from preeclampsia pregnancies relative to CVS from healthy pregnancies. The 1st trimester trophoblast cell line, HTR8/SVneo, was used to investigate the relationship between hypoxia and Notch signaling in trophoblast migration and invasion. RNA sequencing and quantitative RT-PCR analyses show that exposure to hypoxia (2.5% O2) activates Notch signaling in HTR-8/SVneo. We demonstrate that exposure of HTR-8/SVneo to hypoxia induces expression of genes associated with cellular migration and invasion and increases HTR-8/SVneo cellular migration and invasion, whereas inhibition of gamma-secretase decreases Notch signaling and decreases HTR-8/SVneo migration and invasion. Analysis of RNA sequencing data from CVS of preeclampsia and uncomplicated pregnancies identified significant differentially expressed genes that are involved in cellular migration and invasion. Decreased expression of migration and invasion genes in CVS from preeclampsia pregnancies, may impair trophoblast migration and invasion in the 2nd trimester of pregnancy, resulting in the development of preeclampsia.
2021-08-05 | GSE155750 | GEO
Project description:Preeclampsia is associated with reduced ISG15 levels impairing extravillous trophoblast invasion.
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Project description:Background: Preeclampsia (PE) is a serious complication of pregnancy characterized by hypertension and organ dysfunction. The pathogenesis involves impaired trophoblast invasion and inadequate spiral artery remodeling, but the exact molecular mechanisms are not fully understood. Methods: This study aimed to investigate the role of arylacetamide deacetylase (AADAC) in the pathogenesis of PE and its effects on trophoblast function. Placental tissues were collected from 30 PE patients and 15 controls. RNA sequencing was performed for 6 severe PE samples and 6 control samples. AADAC expression in primary trophoblasts was validated via semiquantitative PCR and Western blotting. To investigate AADAC function under hypoxia, HTR8/SVneo cells were treated with CoCl2, and AADAC expression was manipulated through siRNA knockdown and overexpression. Invasion and tube formation assays were conducted to assess trophoblast function. Results: RNA sequencing revealed upregulated AADAC expression in placental tissue from PE patients. AADAC mRNA levels were significantly greater in placental cells from PE patients than in those from controls (p<0.01), whereas AADAC protein expression was lower (p<0.01). Subjecting HTR8/SVneo cells to hypoxia for 18 hours significantly increased AADAC mRNA and protein expression (p<0.001) and HIF1-alpha protein levels (p<0.05). Compared with those in control cells, the invasion (p<0.01) and tube formation (p<0.01) of hypoxia-treated HTR8/SVneo cells were greater after AADAC silencing. AADAC overexpression reduced tube formation (p<0.001) but did not significantly affect invasion. Conclusions: This study demonstrated that under hypoxic conditions, AADAC expression is significantly altered in human PE placental tissues and may play a role in trophoblast invasion and angiogenesis, which are key processes in the pathogenesis of PE. While further research is needed to elucidate the underlying mechanisms and confirm its clinical relevance, these findings suggest that AADAC could be a potential factor involved in the management of PE.
2025-08-28 | GSE306283 | GEO
Project description:Abnormal placentation is a fundamental cause of pregnancy complications including preeclampsia, miscarriage, and intrauterine growth restriction. Proliferation, differentiation, migration, and invasion are key properties of trophoblast cells that regulate trophoblast functions. Imbalance of these cellular processes is linked to placental pathologies. Using HTR-8/SVneo immortalized human trophoblast cells, we demonstrate that steroid receptor coactivator-2 (SRC-2), a transcriptional regulator of nuclear receptors, is essential for extravillous trophoblast cell proliferation, migration, and invasion. Genome-wide transcriptomics identified an SRC-2–dependent transcriptome in HTR-8/SVneo cells that includes a diverse spectrum of proteins involved in placental tissue development and function. To emphasize the utility of this transcriptomics data set, we demonstrate that WNT family member 9A (WNT9A) is not only a molecular target of SRC-2 but also crucial for maintaining many of the cellular properties of human extravillous trophoblast cells.
2025-07-29 | GSE278677 | GEO
Project description:miR-515-5p suppresses trophoblast cell invasion and proliferation through XIAP regulation in preeclampsia
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Project description:Silencing AADAC enhances trophoblast invasion and reveals a protective angiogenic role in severe preeclampsia
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Project description:MicroRNAs (miRNAs) are non-coding small RNA molecules that can be secreted into the circulation and which exist in remarkably stable forms. Circulating miRNAs regulates numerous regulations of biological process and aberrantly expressed in pathological status. Differentially expressed circulating miRNAs have received attention as potential biomarkers for many diseases. In this study, we revealed that miR-515-5p was significantly upregulated in maternal serum from preeclampsia (PE) patients in comparison to normal pregnant women. Bioinformatics prediction and a dual-luciferase reporter gene assay revealed that miR-515-5p directly targets the X-linked inhibitor of apoptosis protein (XIAP) 3’-untranslated region (UTR). Furthermore, the XIAP mRNA expression was decreased in the preeclamptic placenta in comparison to that in normal pregnancy. The overexpression of miR-515-5p inhibited the proliferation and invasion of HTR-8/SVneo trophoblast cells. Collectively, miR-515-5p may play critical roles in the pathogenesis of PE through suppression of the expression of XIAP and serum miR-515-5p may act as a potential biomarker for PE
2022-06-26 | GSE206763 | GEO
Project description:Comparison of genes associated with the EMT between undifferentiated cytotrophoblast cells (CTB) and differentiated extravillous trophoblast cells (EVT) from third trimester human placenta. Cells isolated from control (placenta previa) and cases (preeclampsia). Cells isolated by immunomagnetic separation using anti-integrin beta4 antibody to purify CTB and anti-HLA-G antibody to purify EVT.
2022-02-26 | GSE188313 | GEO
Project description:Diminished trophoblast differentiation in early onset preeclampsia
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