Neural stem cell-derived exosomes suppress neuronal cell apoptosis by activating autophagy via miR-374-5p/STK-4 axis in spinal cord injury.
Lin Zhang, Pengbo Han
Abstract
OBJECTIVES: To evaluate the roles of MicroRNAs (miRNAs) enclosed in the neuron-derived exosomes in the recovery of the spinal cord injury (SCI) and the mechanism. METHODS: treated HT22 cells were used to simulate SCI cells and cocultured with exosomes to analyze the cell apoptosis using TUNEL assays and flow cytometry. Apoptosis- and autophagy-related protein expression was detected by western blot and the green fluorescent protein (GFP)-LC3 assay was used to detect the level of autophagy. In addition, luciferase assay was performed to assess the relationship between miR-374-5p and SKT-4. RESULTS: Exosomes from NSCs alleviated spinal cord injury by triggering autophagy flux and suppressing apoptosis. Besides, miR-374-5p was highly expressed in these exosomes and was responsible for the decent in injured neural cell apoptosis by activating autophagy flux. The SKT-4 was the target gene regulated by miR-374-5p in this exosomal protective function to SCI cells. CONCLUSION: The elevated level of miR-374-5p in neuronal exosomes could enhance spinal cord injury recovery by activating autophagy.