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 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.
Department of Neurology, Huadong Hospital, Fudan University, Shanghai, China.
Li
L
Zhang
Lian-Yan
LY
Dong
Ya-Jian
YJ
Li
Zhen
Z
Hong
Wen-Shi
WS
Wei
D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology; D053222:Fas Ligand Protein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D017628:Microglia / Q000502:physiology*; D009474:Neurons / Q000473:pathology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000502:physiology
D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D035683:MicroRNAs; C546082:mirn21 microRNA, rat