NDRG2 promoted secreted miR-375 in microvesicles shed from M1 microglia, which induced neuron damage.
Biochem Biophys Res Commun
; 469(3): 392-8, 2016 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-26631961
ABSTRACT
BACKGROUND:
Microglia microvesicles (MVs) has shown to have significant biological functions under normal conditions. A diversity of miRNAs is involved in neuronal development, survival, function, and plasticity, but the exact functional role of NDRG2 and secreted miR-375 in MVs in neuron damage is poorly understood. We investigated the effect of NDRG2 and secreted miR-375 in MVs shed from M1 microglia on neuron damage.METHODS:
Expression of Nos2, Arg-1, miR-375, syntaxin-1A, NDRG2 and Pdk 1 were evaluated using RT-PCR or western blotting. Cell viability of N2A neuron was quantified by a MTT assay.RESULTS:
Microglia can be polarized into different functional phenotypes. Expression of NDRG2 and Nos2 were significantly increased by LPS treatment on N9 cells, whereas treatment with IL-4 dramatically suppressed the expression of NDRG2 and remarkably elevated expression of Arg-1. Besides, MVs shed from LPS-treated N9 microglia significantly inhibited cell viability of N2A neurons and expression of syntaxin-1A, and NDRG2 interference reversed the up-regulated miR-375 in LPS-treated N9 microglia and MVs shed from LPS-treated N9 cells. Furthermore, NDRG2 could modulate miR-375 expression in N9 microglia and MVs. And miR-375 inhibitor remarkably elevated Pdk1 expression in N2A neurons. Finally, miR-375 inhibitor could reverse suppression effect of NDRG2 overexpression on cell viability of N2A neurons and expression of syntaxin-1A.CONCLUSION:
Our results demonstrated that NDRG2 promoted secreted miR-375 in microvesicles shed from M1 microglia, which induced neuron damage. The suppression of NDRG2 and secreted miR-375 in MVs shed from M1 microglia may be potential targets for alleviation of neuron damage.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Microglia
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MicroRNAs
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Micropartículas Derivadas de Células
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Proteínas do Tecido Nervoso
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Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article