Conclusion
Collectively, exosomal miR-181c-3p derived from cortical neurons exerts protective effects on neuroinflammation in astrocytes via downregulation of CXCL1 in an IBI rat model.
Methods
An IBI rat model was established by middle cerebral artery occlusion (MCAO). Astrocytes collected from rats were exposed to exosomes derived from cortical neurons to investigate the effect of exosomes on chemokine (C-X-C motif) ligand 1 (CXCL1) expression and inflammatory response. Then, ectopic expression was induced in astrocytes treated with oxygen and glucose deprivation (OGD).
Results
CXCL1 was identified to be an upregulated gene in IBI by microarray-based gene expression profiling. Additionally, upregulation of CXCL1 and promoted inflammatory response was also found in MCAO rats. miR-181c-3p was downregulated in OGD-treated cortical neurons and exosomes derived from OGD-treated cortical neurons. Exosomes derived from OGD-treated cortical neurons decreased the expression of CXCL1 and inflammatory factors in astrocytes, and exosomes delivered miR-181c-3p to decrease CXCL1 expression in astrocytes. CXCL1 was a target gene of miR-181c-3p. Delivery with miR-181c-3p mimic and siRNA against CXCL1 (si-CXCL1) was shown to inhibit inflammation in astrocytes by downregulating CXCL1.