Upregulation of UBAP2L in Bone Marrow Mesenchymal Stem Cells Promotes Functional Recovery in Rats with Spinal Cord Injury

Abstract

Post-translational modifications of cellular proteins with ubiquitin or ubiquitin-like proteins regulate many cellular processes, such as cell proliferation, differentiation, apoptosis, signal transduction, intercellular immune recognition, inflammatory response, stress response, and DNA repair. Nice4/UBAP2L is an important member in the family of ubiquitin-like proteins, and its biological function remains unknown. This study aimed to investigate the effect of UBAP2L on spinal cord injury (SCI). At first, rat bone marrow mesenchymal stem cells (BMSCs) were infected with adeno-associated virus to induce over-expression of Nice4. Subsequently, the infected BMSCs were transplanted into rats suffering from semi-sectioned SCI. The results showed that the over-expression of Nice4 significantly promoted the proliferation and differentiation of BMSCs. In addition, the transplantation of infected BMSCs into the injured area of SCI rats improved the function repair of SCI. Importantly, the immunohistochemical and hematoxylin-eosin staining and RT-PCR results showed that the number of neuronal cells, oligodendrocytes, and astrocytes was significantly increased in the injured area, along with significantly upregulated expression of cyclin D1 and p38 mitogen-activated protein kinase (MAPK). Meanwhile, the expression of caspase 3 protein was significantly down-regulated. In conclusion, the over-expression of Nice4 gene can promote the functional recovery in SCI rats by promoting cell proliferation and inhibiting apoptosis. The results of this study indicate an alternative option for the clinical treatment of SCI.

Keywords

bone marrow mesenchymal stem cells / spinal cord injury / ubiquitin-associated protein 2-like / apoptosis / proliferation

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