miR-21 represses FasL in microglia and protects against microglia-mediated neuronal cell death following hypoxia/ischemia

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...

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Bibliographic Details
Published in:Glia 2012-12, Vol.60 (12), p.1888-1895
Main Authors: Zhang, Li, Dong, Lian-Yan, Li, Ya-Jian, Hong, Zhen, Wei, Wen-Shi
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Cell Death - physiology
Cell Hypoxia - physiology
Cells, Cultured
Down-Regulation - physiology
Fas Ligand Protein - antagonists & inhibitors
Fas Ligand Protein - biosynthesis
Fas Ligand Protein - genetics
FasL
HEK293 Cells
Humans
hypoxia
microglia
Microglia - physiology
microRNA
MicroRNAs - physiology
neuronal apoptosis
Neurons - pathology
Neurons - physiology
Rats
Rats, Sprague-Dawley
Up-Regulation - physiology
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Summary: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. © 2012 Wiley Periodicals, Inc.
ISSN:0894-1491
1098-1136
DOI:10.1002/glia.22404