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

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

  • Mol Neurobiol. 2022 Jan;59(1):429-444. doi: 10.1007/s12035-021-02607-3.
Ying Zou 1 2,  Jiaqi Zhang 1 2,  Jingmin Liu 1 2,  Jiawei Xu 1 2,  Lanya Fu 1 2,  Xinrui Ma 1 2,  Yizhou Xu 1 2 3,  Shuyi Xu 1 2,  Xianghai Wang 1 2 4,  Jiasong Guo 5 6 7 8 9
Affiliations

Affiliations

  • 1 Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • 2 Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, 510515, China.
  • 3 Department of Spine Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
  • 4 Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, 510700, China.
  • 5 Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China. [email protected].
  • 6 Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, 510515, China. [email protected].
  • 7 Department of Spine Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China. [email protected].
  • 8 Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, 510700, China. [email protected].
  • 9 Key Laboratory of Mental Health of the Ministry of EducationGuangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangzhou, 510515, China. [email protected].
PMID: 34708329 DOI: 10.1007/s12035-021-02607-3
Abstract

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.

Keywords

Dedifferentiation; Peripheral nerve injury; SIRT6; Schwann cells; Wallerian degeneration; c-Jun.

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