Apoptotic exosome-like vesicles regulate endothelial gene expression, inflammatory signaling, and function through the NF-κB signaling pathway
| Autor: | Francis Migneault, Alexandre Brodeur, Nicolas Thibodeau, Mélanie Dieudé, Marie-Pierre Hardy, Deborah Beillevaire, Claude Perreault, Julie Turgeon, Marie-Josée Hébert |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
CD31
lcsh:Medicine Apoptosis Inflammation Exosomes Exosome Article Extracellular Vesicles 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Human Umbilical Vein Endothelial Cells medicine Humans Gene silencing Endothelial dysfunction lcsh:Science 030304 developmental biology 0303 health sciences Multidisciplinary Chemistry lcsh:R NF-kappa B Endothelial Cells medicine.disease Cell biology Platelet Endothelial Cell Adhesion Molecule-1 030220 oncology & carcinogenesis Extracellular signalling molecules lcsh:Q medicine.symptom Signal transduction |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-15 (2020) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-69548-0 |
| Popis: | Persistent endothelial injury promotes maladaptive responses by favoring the release of factors leading to perturbation in vascular homeostasis and tissue architecture. Caspase-3 dependent death of microvascular endothelial cells leads to the release of unique apoptotic exosome-like vesicles (ApoExo). Here, we evaluate the impact of ApoExo on endothelial gene expression and function in the context of a pro-apoptotic stimulus. Endothelial cells exposed to ApoExo differentially express genes involved in cell death, inflammation, differentiation, and cell movement. Endothelial cells exposed to ApoExo showed inhibition of apoptosis, improved wound closure along with reduced angiogenic activity and reduced expression of endothelial markers consistent with the first phase of endothelial-to-mesenchymal transition (endoMT). ApoExo interaction with endothelial cells also led to NF-κB activation. NF-κB is known to participate in endothelial dysfunction in numerous diseases. Silencing NF-κB reversed the anti-apoptotic effect and the pro-migratory state and prevented angiostatic properties and CD31 downregulation in endothelial cells exposed to ApoExo. This study identifies vascular injury-derived extracellular vesicles (ApoExo) as novel drivers of NF-κB activation in endothelial cells and demonstrates the pivotal role of this signaling pathway in coordinating ApoExo-induced functional changes in endothelial cells. Hence, targeting ApoExo-mediated NF-κB activation in endothelial cells opens new avenues to prevent endothelial dysfunction. |
| Databáze: | OpenAIRE |
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