Dynamic release of neuronal extracellular vesicles containing miR-21a-5p is induced by hypoxia
Korvenlaita, Nea (A.I. Virtanen Institute for Molecular Sciences)
Gómez-Budia, Mireia (A.I. Virtanen Institute for Molecular Sciences)
Scoyni, Flavia (A.I. Virtanen Institute for Molecular Sciences)
Pistono, Cristiana (A.I. Virtanen Institute for Molecular Sciences)
Giudice, Luca (University of Verona)
Eamen, Shaila (A.I. Virtanen Institute for Molecular Sciences)
Loppi, Sanna (University of Arizona)
de Sande, Ana Hernández (A.I. Virtanen Institute for Molecular Sciences)
Huremagic, Benjamin (KU Leuven)
Bouvy-Liivrand, Maria (University of Eastern Finland. School of Medicine)
Heinäniemi, Merja (School of Medicine)
Kaikkonen, Minna U. (A.I. Virtanen Institute for Molecular Sciences)
Cheng, Lesley (La Trobe University)
Hill, Andrew F. (Victoria University)
Kanninen, Katja M. (A.I. Virtanen Institute for Molecular Sciences)
Jenster, Guido W. (Erasmus University Medical Center)
van Royen, Martin E. (Erasmus University Medical Center)
Ramiro, Laura (Universitat Autònoma de Barcelona)
Montaner, Joan (Hospital Universitario Virgen Macarena (Sevilla, Andalusia))
Batkova, Tereza (St. Anne's University Hospital and Masaryk University)
Mikulik, Robert (St. Anne's University Hospital and Masaryk University)
Giugno, Rosalba (University of Verona)
Jolkkonen, Jukka (A.I. Virtanen Institute for Molecular Sciences)
Korhonen, Paula (A.I. Virtanen Institute for Molecular Sciences)
Malm, Tarja (A.I. Virtanen Institute for Molecular Sciences)

Date:	2023
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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Biomarkers ; Extracellular vesicle ; Hypoxia ; Ischemic stroke ; Mir-21a-5p ; Neuron
Published in:	Journal of extracellular vesicles, Vol. 12 (january 2023) , ISSN 2001-3078

DOI: 10.1002/jev2.12297
PMID: 36594832

21 p, 5.5 MB

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