Exosomal miR-409-3p secreted from activated mast cells promotes microglial migration, activation and neuroinflammation by targeting Nr4a2 to activate the NF-κB pathway

• DOI: 10.1186/s12974-021-02110-5
• Publication Date: 2021-03-09T14:03:05Z
• Authors: Liuqing Hu; Linjie Si; Xiaonan Dai; Hongquan Dong; Zijian Ma; Zhaochu Sun; Nana Li; Huanhuan Sha; Yinan Chen; Yanning Qian; Zhiyuan Zhang
• Keywords: CD86; Exosome

Abstract Objective Neuroinflammation plays a critical role in central nervous system diseases. Exosomal miRNAs released from various cells are implicated cell-to-cell communication. Prior studies have placed substantial emphasis on the of cytokines mast cell-microglia interactions during neuroinflammation. However, it has never been clearly determined whether exosomal participate interaction between and microglia thus mediate Methods The characteristics exosomes isolated cell culture supernatants were confirmed by transmission electron microscopy (TEM), nanoparticle-tracking analysis (NTA) Western blot. transfer PKH67-labelled Cy3-labelled miR-409-3p was observed fluorescence microscopy. Migration activation murine BV-2 microglial evaluated through Transwell assays immunofluorescence staining for Iba1 CD68. CD86, IL-1β, IL-6 TNF-α assessed via qRT-PCR ELISA. MiR-409-3p detected qRT-PCR. Nr4a2 NF-κB levels measured western Regulatory effects identified luciferase reporter assays. Results Lipopolysaccharide (LPS)-stimulated P815 secreted that efficiently taken up cells, which promoted migration activation. LPS-P815 increased microglia. Furthermore, activated delivered to Upregulated migration, neuroinflammation targeting activate pathway. Conclusion promotes pathway, provides evidence not only but also In future, may provide new insights into