The decreased expression of miR-429 in plasma exosomes after spinal cord injury inhibits neuronal apoptosis by mediating the PTEN/PI3K/Akt pathway.

Abstract

BackgroundNeuronal apoptosis after spinal cord injury (SCI) leads to sensorial and motorial dysfunction. Exosomes are vesicles that contain many cellular components, including microRNA, and the role of miR-429 in plasma exosomes in this process after SCI requires further investigation.MethodsThe New York University impactor was used to create a rat model of SCI. We used SH-SY5Y cells to construct a neuronal apoptotic cell model and extracted plasma exosomes from rats in a stimulation. A miR-429 mimic and inhibitor were transfected, and the apoptosis-related indicators of the SH-SY5Y cells were detected by using western blot, cell-counting kit-8 and immunofluorescence. The possible targets of miR-429 were examined to verify the pathway of action. We then used the dual-luciferase reporter assay to verify the binding of miR-429 with downstream molecules and speculate the mechanism of action.ResultsWe successfully isolated and identified exosomes from plasma. Both the mean of adding exosomes extracted from SCI-patients’ plasma and knockdown of miR-429 in the culture of SH-SY5Y cells promoted their apoptosis. Dual luciferase assays confirmed the interaction of miR-429 and 3'-UTR region of phosphatase and tensin homolog (PTEN), which is the downstream target gene of miR-429, and the knockdown of miR-429 inhibits the phosphoinositide 3-kinase/protein kinase B pathway by upregulating PTEN.ConclusionsOur study showed that the decreased expression of miR-429 in SCI rat plasma exosomes promotes the apoptosis of nerve cells, which may be achieved by miR-429 interacting with PTEN and then affecting the PI3K/Akt pathway. This can be a possible mechanism of damage caused by SCI.