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

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...

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Authors: Korvenlaita, Nea, Gómez-Budia, Mireia, Scoyni, Flavia, Pistono, Cristiana, Giudice, Luca, Eamen, Shaila, Loppi, Sanna|||0000-0002-8848-0453, de Sande, Ana Hernández, Huremagic, Benjamin, Bouvy-Liivrand, Maria|||0000-0002-1375-3218, Heinäniemi, Merja, Kaikkonen, Minna U., Cheng, Lesley, Hill, Andrew F., Kanninen, Katja M., Jenster, Guido|||0000-0002-8658-2552, Van Royen, Martin E., Ramiro, Laura|||0000-0002-4121-4609, Montaner, Joan|||0000-0003-4845-2279, Batkova, Tereza, Mikulik, Robert, Giugno, Rosalba, Jolkkonen, Jukka, Korhonen, Paula, Malm, Tarja
Format: article
Publication Date:2023
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:270741
Online Access:https://ddd.uab.cat/record/270741
https://dx.doi.org/urn:doi:10.1002/jev2.12297
Access Level:Open access
Keyword:Biomarkers
Extracellular vesicle
Hypoxia
Ischemic stroke
Mir-21a-5p
Neuron
Description
Summary: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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