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Publication details
Dynamic release of neuronal extracellular vesicles containing miR-21a-5p is induced by hypoxia
Authors | |
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Year of publication | 2023 |
Type | Article in Periodical |
Magazine / Source | Journal of Extracellular Vesicles |
MU Faculty or unit | |
Citation | |
web | https://onlinelibrary.wiley.com/doi/10.1002/jev2.12297 |
Doi | http://dx.doi.org/10.1002/jev2.12297 |
Keywords | biomarkers; extracellular vesicle; hypoxia; ischemic stroke; miR-21a-5p; neuron |
Description | 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. |