Metabolism-related MOGS Gene is Dysregulated After Peripheral Nerve Injury and Negatively Regulates Schwann Cell Plasticity

Cellular metabolism is essentially linked to tissue remodeling and organ regeneration. MOGS, a gene that encodes cellular metabolism-related protein mannosyl-oligosaccharide glucosidase, was found to be upregulated in nerve segments after peripheral nerve injury. Bioinformatic analyses identified upstream regulators of MOGS and MOGS-associated genes and indicated the significant involvement of cellular metabolism in peripheral nerve regeneration. Functional assessment showed that siRNA-mediated knockdown of MOGS led to elevated proliferation, migration, and differentiation of Schwann cells, indicating the negative regulation of MOGS on Schwann cell plasticity. Schwann cells transfected with MOGS siRNA also showed lower expression of fatty acid synthase (FASN), demonstrating that dysregulated MOGS in Schwann cells may affect neuronal behavior through the metabolic coupling between Schwann cells and axons. Taken together, this study demonstrated that MOGS may be a key regulating factor of Schwann cells and neuronal phenotype during peripheral nerve regeneration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12031-022-02024-8.