Detalle Publicación

Cardiac progenitor cell exosomal miR-935 protects against oxidative stress

Autores: Aguilar, S.; García Olloqui, Paula; Amigo-Morán, L.; Torán, J. L.; López, J. A.; Albericio, G.; Abizanda Sarasa, Gloria María; Herrero, D.; Vales Aranguren, África; Rodríguez Díaz, Saray; Higuera, M.; García-Martín, R.; Vázquez, J.; Mora, C.; González-Aseguinolaza, G.; Prosper Cardoso, Felipe; Pelacho Samper, Beatriz (Autor de correspondencia); Bernad, A. (Autor de correspondencia)
Título de la revista: CELLS
ISSN: 2073-4409
Volumen: 12
Número: 18
Páginas: 2300
Fecha de publicación: 2023
Resumen:
Oxidative stress-induced myocardial apoptosis and necrosis are critically involved in ischemic infarction, and several sources of extracellular vesicles appear to be enriched in therapeutic activities. The central objective was to identify and validate the differential exosome miRNA repertoire in human cardiac progenitor cells (CPC). CPC exosomes were first analyzed by LC-MS/MS and compared by RNAseq with exomes of human mesenchymal stromal cells and human fibroblasts to define their differential exosome miRNA repertoire (exo-miRSEL). Proteomics demonstrated a highly significant representation of cardiovascular development functions and angiogenesis in CPC exosomes, and RNAseq analysis yielded about 350 different miRNAs; among the exo-miRSEL population, miR-935 was confirmed as the miRNA most significantly up-regulated; interestingly, miR-935 was also found to be preferentially expressed in mouse primary cardiac Bmi1+high CPC, a population highly enriched in progenitors. Furthermore, it was found that transfection of an miR-935 antagomiR combined with oxidative stress treatment provoked a significant increment both in apoptotic and necrotic populations, whereas transfection of a miR-935 mimic did not modify the response. Conclusion. miR-935 is a highly differentially expressed miRNA in exo-miRSEL, and its expression reduction promotes oxidative stress-associated apoptosis. MiR-935, together with other exosomal miRNA members, could counteract oxidative stress-related apoptosis, at least in CPC surroundings.
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