<<< Full experiment listing

PXD051697

PXD051697 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePlacental growth factor mediates pathological uterine vasculature by activating the NFAT5-SGK1 mechano-signaling axis in the endometrium: Implications for pre-eclampsia development.
DescriptionAfter menstruation the uterine spiral arteries are repaired through angiogenesis. This process is tightly regulated by the paracrine communication between endometrial stromal cells (EnSCs) and endothelial cells. Any molecular aberration in these processes can lead to complications in pregnancy including miscarriage or pre-eclampsia (PE). Placental growth factor (PlGF) can increase cell stiffness contributing to pathological angiogenesis but the biomechanisms remain poorly understood. In this study, we investigated whether PlGF contributes to pathological uterine vasculature by disrupting EnSCs and endothelial paracrine communication. We observed that PlGF mediates a tonicity-independent activation of nuclear factor of activated T cells 5 (NFAT5) in EnSCs. NFAT5 activated downstream targets including SGK1, HIF-1α and VEGF-A. In depth characterization of PlGF - conditioned medium (CM) from EnSCs using mass spectrometry and ELISA methods revealed low VEGF-A and an abundance of extracellular matrix organization associated proteins. Secreted factors in PlGF-CM impeded normal angiogenic cues in endothelial cells (HUVECs) by downregulating Notch-VEGF signalling. Interestingly, PlGF-CM failed to support human placental (BeWo) cell invasion through HUVEC monolayer. Inhibition of SGK1 in EnSCs improved angiogenic effects in HUVECs and promoted BeWo invasion, revealing SGK1 as a key intermediate player modulating PlGF mediated anti-angiogenic signalling. Taken together, perturbed PlGF-NFAT5-SGK1 mechano-signaling in the endometrium can contribute to pathological uterine angiogenesis by negatively regulating EnSCs -endothelial crosstalk resulting in poor quality vessels in the uterine microenvironment. Taken together the signaling may impact on normal trophoblast invasion and thus placentation and, may be associated with an increased risk of complications such as PE.
HostingRepositoryPRIDE
AnnounceDate2024-10-17
AnnouncementXMLSubmission_2024-10-17_02:38:54.515.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAna Velic
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-04-24 02:57:16ID requested
12024-10-17 02:38:55announced
Publication List
Raja Xavier JP, Okumura T, Apweiler M, Chacko NA, Singh Y, Brucker SY, Takeda S, Lang F, Salker MS, Placental growth factor mediates pathological uterine angiogenesis by activating the NFAT5-SGK1 signaling axis in the endometrium: implications for preeclampsia development. Biol Res, 57(1):55(2024) [pubmed]
10.1186/s40659-024-00526-w;
Keyword List
submitter keyword: pre-eclampsia, endometrium, SGK1, pregnancy, placentation, mechanobiology,PlGF
Contact List
Dr. Madhuri Salker
contact affiliationForschungsinstitut für Frauengesundheit Universitäts- Frauenklinik Universitätsklinikum Tübingen Germany
contact emailMadhuri.Salker@med.uni-tuebingen.de
lab head
Ana Velic
contact affiliationUniversity of Tuebingen
contact emaila.velic@uni-tuebingen.de
dataset submitter
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/10/PXD051697
PRIDE project URI
Repository Record List
[ + ]