Endocytosis-associated patterns in nerve regeneration after peripheral nerve injury

Guidong Shi; Dingyu Hao; Lei Zhang; Jia Qin; Guangyuan Tian; Boyuan Ma; Xianhu Zhou

doi:10.1016/j.jot.2021.09.004

Endocytosis-associated patterns in nerve regeneration after peripheral nerve injury

J Orthop Translat. 2021 Oct 21:31:10-19. doi: 10.1016/j.jot.2021.09.004. eCollection 2021 Nov.

Authors

Guidong Shi^{1

2}, Dingyu Hao³, Lei Zhang³, Jia Qin³, Guangyuan Tian³, Boyuan Ma³, Xianhu Zhou⁴

Affiliations

¹ Department of Orthopaedics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
² Shandong University Centre for Orthopaedics, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
³ Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China.
⁴ The Affiliated Hospital of Medical School, Ningbo University, 247 People Road, Jiangbei District, Ningbo, Zhejiang, China.

Abstract

Background: Clearance of myelin debris and remyelination of myelin are necessary steps for peripheral nerve remodeling and regeneration. It has yet to be clarified which genes or proteins are involved in endocytosis or exocytosis in the removal of myelin debris during peripheral nerve repair.

Methods: For this project, a rat model of subacute stage of sciatic nerve injury was established first. Subsequently, normal Schwann cells (NSCs) and activated Schwann cells (ASCs) were harvest before and after peripheral nerve injury (PNI). Following methylated DNA immunoprecipitation sequencing (MeDIP-seq) and tandem mass tags (TMT) labeling analysis of NSCs and ASCs, what common biomarkers changes in peripheral nervous systems remain to be elucidated.

Results: A total of 14,770 different expression genes (DEGs) and 3249 different expression proteins (DEPs) were screened between ASCs and NSCs. For the exosomes, the diameter and particles concentration of exosomes were 141.7 nm and 2.97 × 10⁷ particles/mL, respectively. The size distribution of exosomes was 50-200 nm. ASCs showed higher cellular uptake ability than the NSCs by cellular uptake test. Moreover, RAB7A, ARF6, ARF1, VPS45, RAB11A, DNM3, and NEDD4 were the core markers and may control the molecular mechanism of the Endocytosis pathway.

Conclusion: These biomarkers may play significant roles in the initiation phase of demyelination and axon regeneration.

The translational potential of this article: This study explores that the endocytosis-associated patterns of Schwann cells may be new therapeutic strategy for nerve tissue engineering and nerve regeneration.

Keywords: Demyelination; Endocytosis; Exocytosis; Nerve regeneration; Peripheral nerve injury; Schwann cells.