Upregulation Of MiR-152Inhibits The Growth Of The Neurites After Spinal Cord Injury

spinal cord injury(SCI), which is caused by lateral bending, dislocation,rotation, axial loading and hyperflexion or hyperextension of the spinal cord, leadto dysfunction of locomotion and paralysis. SCI is a disease of the highmortality rate and poor prognosis. An estimated2.5million people live withSCI in the world. The SCI patients bring the emotionally and financiallyenormous burdens to themselves and their families and society.The pathological process of SCI chronologically consists of the primaryinjury and secondary injury. The primary injury refers to the local destroyedspinal cord by mechanical force directly, such as compression, distraction,laceration and transection. The secondary injury extended from the nidus sets inminutes after SCI and lasts for weeks or mouths. Some events of the secondinjury consist of electrolyte shifts, oedema, free radicals, delayed calcium influx,inflammation and necrotic/apoptotic cell death. The mild primary injury elicitsfewer inflammatory and following secondary injuries than the moderate or severeinjury. The severity of the primary injury largely determines a patient’sneurological grade. The therapeutic strategies of SCI have focused on combating the secondary detrimental factors, such as stimulating axonalregeneration, suppressing self-perpetuating degeneration, and theregenerative neurons and glia functionally integrate into the survivingneural tissue. The destroyed nerve fibers and contact among cells, which theprimary and secondary lead to, interfere incoming and outgoing informationtransfer in the bilateral damaged area. Enhance the ability of regeneration ofnerve fibers partly improve the integration and transfer of sensory and motorinformation, and promote functional recovery after SCI.Compare to the ability of dorsal root ganglion neurons in adult PNS, theneurons contain the limited ability of axonal regeneration in the adult CNS.Despite the many extent factors that inhibitor axonal growth, the ability ofspontaneous axonal regeneration is a very important intrinsic factor. Differencesin spontaneous regeneration ability between CNS and PNS are related with themolecular differences.microRNAs(miRNAs) are a class of short non-coding RNA, which suppressthe expression of the target genes in post-transcriptional negative regulation bycombination with3’ UTR of target genes. A miRNA may be involved inregulation of multiple target genes. In the miRNA microarray of the traumaticspinal cord, we found that the expression levels of some miRNAs changedsignificantly in up-or down-regulation, such as upregulation of miR-152.Real-time quantitative PCR showed the expression of miR-152was elevated afterSCI. In situ hybridization experiments confirmed that of miR-152expression inthe spinal cord gray matter. In the primary cortex neurons culture model ofhypoxic injury, glutamate stimulation, inflammatory stimulation and mechanicalscratches, we found that inflammatory stimulation and mechanical scratches ledto up-regulation of miR-152in vitro. Neurite growth was inhibited in neurons which highly express miR-152. MAP2, Tau, and GAP-43proteins weredownregulated in neurons with the high expression of miR-152. By Targetscansoftware, miR-152target genes were screened and predicted. We focused onseveral target genes which have been reported to be involved in regulatingneuronal outgrowth by other researchers, such as Naa15gene. The dual luciferasedetected Naa15is one of the miR-152target genes. Naa15and Naa10consist ofN-α acetyltransferase. Naa10regulates brain α-tubulin acetylation. It is closelyrelated with α-tubulin acetylation and microtubule stability. N-α acetyl transferaseregulates dendritic growth when the expression level of the Naa10and Naa15were balanced.miR-152suppressed the expression of Naa15which led to theinhibition of dendrite growth. We found miR-152also suppressed the expressionof KLF-6, E2F7and Elavl4which were related with axonal regeneration.Studies of the mechanism of miR-152after SCI can not only furtherunderstand of the roles of the pathophysiological changes of miRNA in neuritegrowth but also provide a new perspective and strategies to SCI treatment.