miR-21 represses FasL in microglia and protects against microglia-mediated neuronal cell death following hypoxia/ischemia.
Glia
; 60(12): 1888-95, 2012 Dec.
Article
em En
| MEDLINE
| ID: mdl-22907769
ABSTRACT
A growing body of evidence suggests that microRNA (miRNA) dysregulation contributes to many types of human disease, including central nervous system disorders. In this study, we identified an inverse correlation between the expression of miR-21 and Fas ligand (FasL) during hypoxia-induced microglial activation. Specifically, hypoxia caused the upregulation of FasL expression but the downregulation of miR-21 expression in microglia. Furthermore, we demonstrated that miR-21 suppresses FasL production by directly binding to its 3'-untranslated region. The overproduction of FasL following hypoxic microglial activation induced neuronal apoptosis, whereas the ectopic expression of miR-21 partially protected neurons from cell death caused by hypoxia-activated microglia. Finally, we confirmed that the function of miR-21 in microglia-mediated neuronal injury is dependent on FasL. Our study demonstrates an important role for miRNAs in microglia-mediated neuronal apoptosis, and suggests potential novel therapeutic interventions for cerebral hypoxic diseases associated with microglial activation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Microglia
/
MicroRNAs
/
Proteína Ligante Fas
/
Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article