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Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability.

ABSTRACT: 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.

SUBMITTER: Rust R

PROVIDER: S-EPMC11318402 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature

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Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability.

Rust Ruslan R Holm Mea M MM Egger Matteo M Weinmann Oliver O van Rossum Daniёlle D Walter Fruzsina R FR Santa-Maria Ana Raquel AR Grönnert Lisa L Maurer Michael A MA Kraler Simon S Akhmedov Alexander A Cideciyan Rose R Lüscher Thomas F TF Deli Maria A MA Herrmann Inge K IK Schwab Martin E ME

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20231124 6

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 s ...[more]

PMID: 38000040

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Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability.

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Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability.

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