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Characterization and Proteomic Analysis of Endometrial Stromal Cell-Derived Small Extracellular Vesicles
- Source :
- The Journal of clinical endocrinology and metabolism. 106(5)
- Publication Year :
- 2020
-
Abstract
- Context Small extracellular vesicles (sEVs) have emerged as modulators of the disease microenvironment, thereby supporting disease progression. However, the potential role of EVs and their content to the pathophysiology of endometriosis remain unclear. Objective This work aimed to investigate whether the EVs from eutopic (Eu) and ectopic (Ec) endometrial stromal cells (ESCs) differ with respect to protein composition and role in endometriosis. Methods Human Eu and Ec endometrium–derived ESCs were isolated from samples of the same patients (n = 3). sEVs were isolated from ESCs via ultracentrifugation; these sEVs were characterized by Western blotting, transmission electron microscopy, and nanoparticle tracking analysis and analyzed using mass spectrometry. The potential role of EcESCs-derived sEVs (EcESCs-sEVs) in endometriosis was explored by assaying their effects on cell viability/proliferation, migration, and angiogenesis. Results In total, 105 ESCs-sEV–associated proteins were identified from EcESCs-sEVs and EuESCs-sEVs by mass spectrometry analysis. The protein content differed between EcESCs-sEVs and EuESCs-sEVs, with annexin A2 (ANXA2) being the most prominent difference—present in EcESCs-sEVs but not EuESCs-sEVs. We also found that sEVs-ANXA2 regulates the motility, proliferation, and angiogenesis of ESCs via the extracellularly regulated kinase (ERK)/STAT3 pathway. Notably, treatment of ESCs with sEVs-ANXA2 resulted in increased proliferation and motility, suggesting that sEVs-ANXA2 may be involved in regulating endometriosis. Our data suggest that EcESCs-sEVs-ANXA2 regulates the motility and the angiogenic potential of ESCs, implying a role for sEVs-ANXA2 in the pathogenesis of endometriosis. Conclusion The study of sEVs-ANXA2 from Ec endometriotic cells uncovers a new mechanism of endometriosis progression and will inform the development of novel therapeutic strategies.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Proteomics
medicine.medical_specialty
Stromal cell
Angiogenesis
viruses
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
Endometriosis
Motility
Context (language use)
Peritoneal Diseases
Biochemistry
03 medical and health sciences
Endometrium
Extracellular Vesicles
0302 clinical medicine
Endocrinology
Cell Movement
Cell-Derived Microparticles
Internal medicine
medicine
Human Umbilical Vein Endothelial Cells
Humans
Viability assay
Annexin A2
Cells, Cultured
Endometrial Stromal Cell
Cell Proliferation
Neovascularization, Pathologic
Chemistry
Biochemistry (medical)
virus diseases
respiratory system
Cell biology
030104 developmental biology
030220 oncology & carcinogenesis
Female
Stromal Cells
Subjects
Details
- ISSN :
- 19457197
- Volume :
- 106
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Accession number :
- edsair.doi.dedup.....e3a75bf079f052d3904a5dd0625d6938