PXD050237

PXD050237 is an original dataset announced via ProteomeXchange.

Title	Effect of aberrant PlGF on endometrial stromal cell actin dynamics : implications in pre-eclampsia.
Description	High levels of placental growth factor (PlGF) are pathological, however its function in endometrial cells remains to be investigated. Cell proliferation and motility requires actin reorganization, which is under the control of various signalling pathways including Rac1 and PAK1 proteins. In this study, we explored whether PlGF induces change in endometrial mechanics by modifying actin cytoskeleton thus contributing to cell stiffness at the maternal interface. To this end, human endometrial stromal cells (EnSCs) were treated with 20 ng/mL for 6 days with PlGF and its influence on cellular mechanics was investigated with atomic force microscopy (AFM), electrical impedance spectroscopy and proteomics methods. Proteomic analysis shows PlGF upregulated RhoGTPases activating proteins and extracellular matrix organization associated proteins. Rac1 and PAK1 transcript levels, activity and actin polymerization were significantly increased with in vitro PlGF treatment. AFM further revealed an increase in cell stiffness with PlGF. The PlGF effect on actin polymerization was inhibited with siRNA- Rac1, PAK1 and WAVE2. PlGF induced cell stiffness was pharmacologically reversed with pravastatin, resulting in improved trophoblast cell invasion as measured using electrical impedance spectroscopy. Thus, PlGF treatment leads to enhanced Rac1 and PAK1 levels, leading to an increase in cell stiffness, impairing trophoblast invasion. Taken together, aberrant PlGF levels can contribute to an altered pre-pregnancy maternal microenvironment and offers a coherent and unifying explanation for the pathological changes observed in pre-eclampsia (PE) conditions.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:46:43.959.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ana Velic
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-29 04:30:44	ID requested
1	2024-06-23 01:19:49	announced
⏵ 2	2024-10-22 06:46:44	announced	2024-10-22: Updated project metadata.

Raja Xavier JP, Rianna C, Hellwich E, Nikolou I, Lankapalli AK, Brucker SY, Singh Y, Lang F, Sch, ä, ffer TE, Salker MS, Excessive endometrial PlGF- Rac1 signalling underlies endometrial cell stiffness linked to pre-eclampsia. Commun Biol, 7(1):530(2024) [pubmed]

10.1038/s42003-024-06220-7;

submitter keyword: actin polymerization, cell stiffness,Endometrial cells, angiogenesis, pre-eclampsia.

Madhuri Salker
contact affiliation	Forschungsinstitut für Frauengesundheit Universitäts- Frauenklinik Uni Tübingen Germany
contact email	Madhuri.Salker@med.uni-tuebingen.de
lab head
Ana Velic
contact affiliation	University of Tuebingen
contact email	a.velic@uni-tuebingen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050237
     1. Label: PRIDE project
     2. Name: Effect of aberrant PlGF on endometrial stromal cell actin dynamics : implications in pre-eclampsia.