Evidence map›Paper›PMID 40632597›Full record

ArticleMolecular human reproduction2025

Identification of transcription factors that regulate placental sFLT1 expression.

Qing Yong, Carin van der Keur, Jacqueline D H Anholts, Hanneke Kapsenberg, Hailiang Mei, Jan A Bruijn, Michael Eikmans, Hans J Baelde

Abstract read
In one paragraph

Article in Molecular human reproduction, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Qing YongDepartment of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.ORCID 0000-0003-0437-271X
Carin van der KeurDepartment of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
Jacqueline D H AnholtsDepartment of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
Hanneke KapsenbergDepartment of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
Hailiang MeiSequencing Analysis Support Core, Leiden University Medical Center, Leiden, The Netherlands.ORCID 0000-0003-1781-5508
Jan A BruijnDepartment of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
Michael EikmansDepartment of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
Hans J BaeldeDepartment of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Increased soluble FMS-like tyrosine kinase 1 (sFLT1) levels have been associated with preeclampsia, chronic kidney diseases, and kidney transplant rejection. However, lower levels of sFLT1 exhibit beneficial properties in various processes, such as the organization of the actin cytoskeleton in podocytes and immune regulation in healthy pregnancy. Therefore, understanding the transcriptional regulation of sFLT-1 and preserving appropriate expression levels are critical for effective treatment of preeclampsia and other diseases. Cytotrophoblasts (CTBs) were isolated from three first-trimester placentas and differentiated into extravillous trophoblasts (EVTs) for 6 days. RNA was extracted at different time points and used for RNA sequencing. Differentially expressed genes (DEGs) and transcription factors (DETFs) were analyzed. Transcription factor (TF) enrichment analysis and pathway analysis were performed on DEGs screened from EVTs and CTBs. TF inhibitors were added to primary CTBs directly or during CTB to EVT differentiation to confirm the regulatory effect of TFs on sFLT1 expression. In total, 197 TFs were differentially expressed between CTBs and EVTs, among which 15 DETFs (EPAS1, ETS1, TBX3, CEBPB, FLI1, TEAD4, GATA4, TBX2, LMX1B, ARNT, FOXM1, ERF, PRDM1, TFAP2A, and NR2F2) that potentially regulate sFLT1 expression were predicted by ChEA3 and KnockTF software. The mRNA levels of 15 DETFs were validated upon CTBs differentiation into both EVTs and syncytiotrophoblasts. The regulatory effects of FOXM1 and CEBPB were confirmed in vitro experiments, and their expression patterns were validated during CTBs differentiation into EVTs and in first-trimester placentas. Pathway analysis showed that FLT1 was involved in P13K-Akt, Rap1, MAPK, Ras, and HIF-1 signaling pathways, focal adhesion, and cytokine-cytokine receptor interaction. Protein-protein interaction analysis showed that FLT4, PDGFB, TGFB1, IL6R, TNFRSF1B, CSF1R, and TGFB2 interact with FLT1. The identified TFs can serve as therapeutic targets in preeclampsia to keep the sFLT1 levels within appropriate limits.

Indexed as

PlacentaTranscription FactorsVascular Endothelial Growth Factor Receptor-1Cell DifferentiationCells, CulturedFemaleGene Expression RegulationHumansPre-EclampsiaPregnancyTrophoblastsFLT1 protein, humanTranscription FactorsVascular Endothelial Growth Factor Receptor-1CEBPBearly pregnancyFOXM1inflammationsoluble FMS-like tyrosine kinase 1transcription factortrophoblast

Identifiers

PMID40632597
PMCPMC12286775

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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.