The compensatory increase of Gli-similar 3 inhibited neuronal apoptosis through regulating Mps one binder kinase activator 1b (MOB1b): a possible strategy for the functional recovery after spinal cord injury.

Abstract

Spinal cord injury (SCI) is a devastating disease characterized by neuronal apoptosis. Gli-similar 3 (GLIS3), a transcriptional factor, was involved in cell apoptosis and associated with the transcription of downstream target genes related to neuronal function. However, the function of GLIS3 in SCI remains unknown. Therefore, we used the mouse model of SCI to explore the role of GLIS3 in SCI. The results showed that GLIS3 expression was significantly increased in spinal cord tissues of SCI mice, and GLIS3 overexpression promoted the functional recovery, reserved histological changes, and inhibited neuronal apoptosis after SCI. Through online tools, the potential target genes of GLIS3 were analyzed and we found that Mps one binder kinase activator 1b (Mob1b) had a strong association with SCI among these genes. MOB1b is a core component of Hippo signaling pathway, which was reported to inhibit cell apoptosis. MOB1b expression was significantly increased in mice at 7 days post-SCI and GLIS3 overexpression further increased its expression. Dual-luciferase reporter assay revealed that GLIS3 bound to the promoter of Mob1b and promoted its transcription. In conclusion, our findings reveal that the compensatory increase of GLIS3 promotes functional recovery after SCI through inhibiting neuronal apoptosis by transcriptionally regulating MOB1b. Our study provides a novel target for functional recovery after SCI.