Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability
In: Journal of Cerebral Blood Flow & Metabolism, 2023
Online
academicJournal
Zugriff:
Nogo-A is a transmembrane protein with multiple functions in the central nervous system (CNS), including restriction of neurite growth and synaptic plasticity. Thus far, Nogo-A has been predominantly considered a cell contact-dependent ligand signaling via cell surface receptors. Here, we show that Nogo-A can be secreted by cultured cells of neuronal and glial origin in association with extracellular vesicles (EVs). Neuron- and oligodendrocyte-derived Nogo-A containing EVs inhibited fibroblast spreading, and this effect was partially reversed by Nogo-A receptor S1PR2 blockage. EVs purified from HEK cells only inhibited fibroblast spreading upon Nogo-A over-expression. Nogo-A-containing EVs were found in vivo in the blood of healthy mice and rats, as well as in human plasma. Blood Nogo-A concentrations were elevated after acute stroke lesions in mice and rats. Nogo-A active peptides decreased barrier integrity in an in vitro blood-brain barrier model. Stroked mice showed increased dye permeability in peripheral organs when tested 2 weeks after injury. In the Miles assay, an in vivo test to assess leakage of the skin vasculature, a Nogo-A active peptide increased dye permeability. These findings suggest that blood borne, possibly EV-associated Nogo-A could exert long-range regulatory actions on vascular permeability. ; ISSN:0271-678X ; ISSN:1559-7016
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Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability
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Autor/in / Beteiligte Person: | Rust, Ruslan ; Holm, Mea M. ; Egger, Matteo ; Weinmann, Oliver ; van Rossum, Daniёlle ; Walter, Fruzsina R. ; Santa-Maria, Ana Raquel ; Grönnert, Lisa ; Maurer, Michael A. ; Kraler, Simon ; Akhmedov, Alexander ; Cideciyan, Rose ; Lüscher, Thomas F. ; Deli, Maria A. ; Herrmann, Inge K. ; Schwab, Martin E. |
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Zeitschrift: | Journal of Cerebral Blood Flow & Metabolism, 2023 |
Veröffentlichung: | SAGE, 2023 |
Medientyp: | academicJournal |
DOI: | 10.3929/ethz-b-000648557 |
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