MiR-182-5p regulates Nogo-A expression and promotes neurite outgrowth of hippocampal neurons in vitro

Abstract

Nogo-A protein is a key myelin-associated inhibitor for axonal growth, regeneration, and plasticity in the central nervous system (CNS). Regulation of the Nogo-A/NgR1 pathway facilitates functional recovery and neural repair after spinal cord trauma and ischemic stroke. MicroRNAs are described as effective tools for the regulation of important processes in CNS such as neuronal differentiation, neuritogenesis, and plasticity. Our results showed that miR-182-5p mimic specifically downregulates the expression of the luciferase reporter gene fused to the mouse Nogo-A 3UTR, and Nogo-A protein expression in Neuro-2a and C6 cells. Finally, we observed that when rat primary hippocampal neurons are co-cultured with C6 cells transfected with miR-182-5p mimic, there is a promotion of the outgrowth of neuronal neurites in length. From all these data we suggest that miR-182-5p may be a potential therapeutic tool for the promotion of axonal regeneration in different diseases of the CNS. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/482803v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@e0979forg.highwire.dtl.DTLVardef@10265eborg.highwire.dtl.DTLVardef@71603dorg.highwire.dtl.DTLVardef@1654818_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIBioinformatics analyses show that miR-182-5p targets Nogo-A 3UTR. C_LIO_LIMiR-182-5p downregulates Nogo-A protein expression in murine cell lines. C_LIO_LIMiR-182-5p promotes neurite outgrowth of rat primary hippocampal neurons in vitro. C_LIO_LIMiR-182-5p is suggested as a potential therapeutic tool for the promotion of axonal regeneration in different pathologies/diseases of the central nervous system. C_LI