Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10815148 | Cellular Signalling | 2015 | 8 Pages |
Abstract
Astrocyte-derived inflammation is a common component of acute or chronic injury in the central nervous system. MicroRNAs (miRNAs) are small non-coding RNAs that play important regulatory roles in the inflammatory response. In this study, we found that miR-206 is induced upon stimulation with lipopolysaccharide. Overexpression of miR-206 in astrocytes led to increased expression of inflammatory cytokines (interleukin-6, interleukin-1β, CCL5) upon exposure to lipopolysaccharide, whereas knockdown of miR-206 had completely opposite effects. We used a combination of bioinformatics and experimental techniques to demonstrate that NR4A2, which belongs to the nuclear receptor (NR) 4 family of orphan nuclear receptors, is a direct target of miR-206. Overexpression of miR-206 mimics decreased the activity of a luciferase reporter containing the NR4A2 3â²-untranslated region and led to decreased NR4A2 mRNA and protein levels. In contrast, ectopic expression of an miR-206 inhibitor led to elevated NR4A2 expression. We also found that miR-206 modulated the lipopolysaccharide-induced proinflammatory response by targeting NR4A2 and activating nuclear factor-kappa B activity. Finally, we demonstrated that the transcription factor AP-1 plays a critical role in lipopolysaccharide-induced expression of miR-206 and that the extracellular signal-regulated kinase signaling pathway contributes to the regulation of miR-206 level in astrocytes. These data demonstrate that miR-206 positively regulates the lipopolysaccharide-induced inflammatory response in human astrocytes.
Keywords
Ccl5UTRextracellular regulated MAP kinasemiRNA recognition elementsMKP-1SOCS-1MRENR4A2NF-κBTLRMUTGAPDHLPSJnkERKMiR-206AstrocyteinflammationToll-like receptormutationbinding sitefull lengthnuclear factor-kappaBlipopolysaccharideMEKuntranslated regionchemokine (C-C motif) ligand 5glyceraldehyde-3-phosphatedehydrogenase
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Authors
Xiaodong Duan, Ali Zohaib, Yunchun Li, Bibo Zhu, Jing Ye, Shengfeng Wan, Qiuping Xu, Yunfeng Song, Huanchun Chen, Shengbo Cao,