Dynamic release of neuronal extracellular vesicles containing miR‐21a‐5p is induced by hypoxia

Autor: Nea Korvenlaita, Mireia Gómez‐Budia, Flavia Scoyni, Cristiana Pistono, Luca Giudice, Shaila Eamen, Sanna Loppi, Ana Hernández deSande, Benjamin Huremagic, Maria Bouvy‐Liivrand, Merja Heinäniemi, Minna U. Kaikkonen, Lesley Cheng, Andrew F. Hill, Katja M. Kanninen, Guido W. Jenster, Martin E. vanRoyen, Laura Ramiro, Joan Montaner, Tereza Batkova, Robert Mikulik, Rosalba Giugno, Jukka Jolkkonen, Paula Korhonen, Tarja Malm
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Extracellular Vesicles, Vol 12, Iss 1, Pp n/a-n/a (2023)
Druh dokumentu: article
ISSN: 2001-3078
DOI: 10.1002/jev2.12297
Popis: Abstract Hypoxia induces changes in the secretion of extracellular vesicles (EVs) in several non‐neuronal cells and pathological conditions. EVs are packed with biomolecules, such as microRNA(miR)‐21‐5p, which respond to hypoxia. However, the true EV association of miR‐21‐5p, and its functional or biomarker relevance, are inadequately characterised. Neurons are extremely sensitive cells, and it is not known whether the secretion of neuronal EVs and miR‐21‐5p are altered upon hypoxia. Here, we characterised the temporal EV secretion profile and cell viability of neurons under hypoxia. Hypoxia induced a rapid increase of miR‐21a‐5p secretion in the EVs, which preceded the elevation of hypoxia‐induced tissue or cellular miR‐21a‐5p. Prolonged hypoxia induced cell death and the release of morphologically distinct EVs. The EVs protected miR‐21a‐5p from enzymatic degradation but a remarkable fraction of miR‐21a‐5p remained fragile and non‐EV associated. The increase in miR‐21a‐5p secretion may have biomarker potential, as high blood levels of miR‐21‐5p in stroke patients were associated with significant disability at hospital discharge. Our data provides an understanding of the dynamic regulation of EV secretion from neurons under hypoxia and provides a candidate for the prediction of recovery from ischemic stroke.
Databáze: Directory of Open Access Journals
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