Informace o publikaci

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

Autoři	KORVENLAITA Nea GOMEZ-BUDIA Mireia SCOYNI Flavia PISTONO Cristiana GIUDICE Luca EAMEN Shaila LOPPI Sanna HERNANDEZ de Sande Ana HUREMAGIC Benjamin BOUVY-LIIVRAND Maria HEINANIEMI Merja KAIKKONEN Minna U CHENG Lesley HILL Andrew F KANNINEN Katja M JENSTER Guido W VAN ROYEN Martin E RAMIRO Laura MONTANER Joan BÁŤKOVÁ Tereza MIKULÍK Robert GIUGNO Rosalba JOLKKONEN Jukka KORHONEN Paula MALM Tarja
Rok publikování	2023
Druh	Článek v odborném periodiku
Časopis / Zdroj	Journal of Extracellular Vesicles
Fakulta / Pracoviště MU	Lékařská fakulta
Citace
www	https://onlinelibrary.wiley.com/doi/10.1002/jev2.12297
Doi	http://dx.doi.org/10.1002/jev2.12297
Klíčová slova	biomarkers; extracellular vesicle; hypoxia; ischemic stroke; miR-21a-5p; neuron
Popis	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.