SGK1 in Schwann cells is a potential molecular switch involved in axonal and glial regeneration during peripheral nerve injury.
Biochem Biophys Res Commun
; 607: 158-165, 2022 06 04.
Article
em En
| MEDLINE
| ID: mdl-35367829
ABSTRACT
Schwann cells play an important role in peripheral myelination, and dysfunction of these cells leads to axonal damage. Schwann cells degenerate following peripheral nerve injury. Immature Schwann cells proliferate, differentiate, and support axonal regeneration and extension during recovery. There are a lot of intracellular signals involved in the myelination process. Although serum- and glucocorticoid-inducible kinase (SGK1) in Schwann cells is supposedly involved in developmental myelination, its significance during peripheral nerve injury and repair remains unknown. In this study, we examined the dynamics of SGK1 during peripheral nerve repair and the potential role of SGK in the process. Axonal crush injury was first generated in the right sciatic nerve under anesthesia in mice, which exhibited apparent paralysis and subsequent recovery of the injured hindlimbs. Immunohistochemical analysis revealed the appearance of glial fibrillary acidic protein (GFAP)-positive immature Schwann cells around injured nerves, and SGK1 was present in these cells. Next, we employed S16 cells, a Schwann cell line, to explore the impact of SGK1 on Schwann cells. Administration of the SGK inhibitor gsk650394 decreased cell proliferation and increased cell size. SGK inhibition did not cause cellular injury, suggesting that it suppresses proliferation and enlarges Schwann cells without causing cell death. Furthermore, quantitative PCR and immunoblotting revealed that SGK inhibition upregulated the gene expression of BDNF, MBP, and Krox20, which are facilitating factors for myelination and neural regeneration, and downregulated that of Sox10. Taken together, these findings indicate that SGK1 inactivation in Schwann cells diverts cell fate from proliferation to differentiation.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Traumatismos dos Nervos Periféricos
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article