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

Korvenlaita, Nea, Gómez-Budia, Mireia, Scoyni, Flavia, Pistono, Cristiana, Giudice, Luca, Eamen, Shaila, Loppi, Sanna, de Sande, Ana Hernández, Huremagic, Benjamin, Bouvy-Liivrand, Maria, Heinäniemi, Merja, Kaikkonen, Minna U, Cheng, Lesley ORCID: 0000-0002-8075-6144, Hill, Andrew F ORCID: 0000-0001-5581-2354, Kanninen, Katja M, Jenster, Guido, van Royen, Martin E, Ramiro, Laura, Montaner, Joan, Batkova, Tereza, Mikulik, Robert, Giugno, Rosalba, Jolkkonen, Jukka, Korhonen, Paula and Malm, Tarja (2023) Dynamic release of neuronal extracellular vesicles containing miR-21a-5p is induced by hypoxia. Journal of Extracellular Vesicles, 12 (1). ISSN 2001-3078


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.

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Item type Article
URI https://vuir.vu.edu.au/id/eprint/47481
DOI 10.1002/jev2.12297
Official URL https://onlinelibrary.wiley.com/doi/10.1002/jev2.1...
Subjects Current > FOR (2020) Classification > 3101 Biochemistry and cell biology
Current > Division/Research > Institute for Health and Sport
Keywords biomarkers; extracellular vesicle; hypoxia; ischemic stroke; miR-21a-5p; neuro
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