Interferon-induced sterile alpha motif and histidine/aspartic acid domain-containing protein 1 expression in astrocytes and microglia is mediated by microRNA-181a.

作者: Changzhong Jin , Xiaorong Peng , Fumin Liu , Linfang Cheng , Tiansheng Xie

DOI: 10.1097/QAD.0000000000001166

关键词: Activator (genetics)ChemistrySterile alpha motifMicrogliaInterferonMolecular biologyPhosphorylationMessenger RNARegulation of gene expressionSignal transduction

摘要: OBJECTIVE Sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1), a newly discovered HIV-1 host restriction factor, has been found to be induced by interferons regulated microRNA-181a (miR-181a). However, the mechanism of interferons-induced SAMHD1 expression is unclear. DESIGN We hypothesized that induce through Janus kinase-signal transducer activator transcription (JAK-STAT) signaling pathways, which mediated miR-181a. METHODS examined effect IFN-α IFN-γ on mRNA expression, as well levels phosphorylated miR-181a in astrocytes microglia. To determine whether was miR-181a, we overexpressed or inhibited these cells exposed them interferons. also detected infection RESULTS Both increased reduced levels, particularly Phosphorylated SAMHD1was not Overexpression counteracted induction interferons, inhibition mimicked treatment. Inhibition JAK-STAT pathways resulted decreased expression. Knock-down overexpression enhanced infection, whereas infection. significantly affected SAMHD1. CONCLUSION MiR-181a an important mediator for microglia, but IFN-α.

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