SIRT6 Negatively Regulates Schwann Cells Dedifferentiation via Targeting c-Jun During Wallerian Degeneration After Peripheral Nerve Injury.

Ying Zou, Jiaqi Zhang, Jingmin Liu, Jiawei Xu, Lanya Fu, Xinrui Ma, Yizhou Xu, Shuyi Xu, Xianghai Wang, Jiasong Guo

Molecular neurobiology 2022 Jan

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Silent information regulator 6 (SIRT6) is a mammalian homolog of the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase sirtuin family. Previous studies have been reported a pro-regenerative role of SIRT6 in central nervous system injury. However, the role of SIRT6 in peripheral nerve injury is still unknown. Given the importance and necessity of Schwann cell dedifferentiation response to peripheral nerve injury, we aim to investigate the molecular mechanism of SIRT6 steering Schwann cell dedifferentiation during Wallerian degeneration in injured peripheral nerve. Herein, we first examined the expression pattern of SIRT6 after peripheral nerve injury. Using the explants of sciatic nerve, an ex vivo model of nerve degeneration, we provided evidences indicating that SIRT6 inhibitor accelerates Schwann cell dedifferentiation as well as axonal and myelin degeneration, while SIRT6 activator attenuates this process. Moreover, in an in vitro Schwann cell dedifferentiation model, we found SIRT6 inhibitor promotes Schwann cell dedifferentiation through upregulating the expression of c-Jun. In addition, downregulation of c-Jun reverse the effects of SIRT6 inhibition on the Schwann cells dedifferentiation and axonal and myelin degeneration. In summary, we first described SIRT6 acts as a negative regulator for Schwann cells dedifferentiation during Wallerian degeneration and c-Jun worked as a direct downstream partner of SIRT6 in injured peripheral nerve. © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Citation

Ying Zou, Jiaqi Zhang, Jingmin Liu, Jiawei Xu, Lanya Fu, Xinrui Ma, Yizhou Xu, Shuyi Xu, Xianghai Wang, Jiasong Guo. SIRT6 Negatively Regulates Schwann Cells Dedifferentiation via Targeting c-Jun During Wallerian Degeneration After Peripheral Nerve Injury. Molecular neurobiology. 2022 Jan;59(1):429-444