Dataset Information

Effect of aberrant PlGF on endometrial stromal cell actin dynamics : implications in pre-eclampsia.

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Ana Velic

LAB HEAD: Madhuri Salker

PROVIDER: PXD050237 | Pride | 2024-06-23

REPOSITORIES: Pride

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			Action	DRS
	20221212_CO_1119MaSa_R13.raw	Raw
	20221212_CO_1119MaSa_R14.raw	Raw
	20221212_CO_1119MaSa_R15.raw	Raw
	20221212_CO_1119MaSa_R16.raw	Raw
	20221212_CO_1119MaSa_R17.raw	Raw

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Publications

Excessive endometrial PlGF- Rac1 signalling underlies endometrial cell stiffness linked to pre-eclampsia.

Raja Xavier Janet P JP Rianna Carmela C Hellwich Emily E Nikolou Iliana I Lankapalli Aditya Kumar AK Brucker Sara Y SY Singh Yogesh Y Lang Florian F Schäffer Tilman E TE Salker Madhuri S MS

Communications biology 20240504 1

Cell stiffness is regulated by dynamic interaction between ras-related C3 botulinum toxin substrate 1 (Rac1) and p21 protein-activated kinase 1 (PAK1) proteins, besides other biochemical and molecular regulators. In this study, we investigated how the Placental Growth Factor (PlGF) changes endometrial mechanics by modifying the actin cytoskeleton at the maternal interface. We explored the global effects of PlGF in endometrial stromal cells (EnSCs) using the concerted approach of proteomics, atom ...[more]

PMID: 38704457

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