GPNMB promotes peripheral nerve regeneration by activating the Erk1/2 and Akt pathways via binding Na+/K+-ATPase α1 in Schwann cells

• Published in: Experimental neurology Vol. 373; p. 114687
• Main Authors: Huang, Chao, Zheng, Yani, Ji, Ruijuan, Qiao, Liang, Zhang, Xi, Lin, Haiyan, Liu, Fang, Xu, Jiajun, Li, Yuquan, Zhang, Zhiying, Yang, Xiangqun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2024
• Subjects: Akt pathway; Erk1/2 pathway; Glycoprotein non-metastatic melanoma protein B; Na+/K+-ATPase α1; Peripheral nerve injury; Regeneration; Schwann cells; Regeneration; Glycoprotein non-metastatic melanoma protein B; Na+/K+-ATPase α1; Schwann cells; Peripheral nerve injury; Erk1/2 pathway; Akt pathway; Na(+)/K(+)-ATPase α1
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2024.114687

Glycoprotein non-metastatic melanoma protein B (GPNMB) is ubiquitously expressed and has protective effects on the central nervous system. In particular, it is also expressed in the peripheral nervous system (PNS) and upregulated after peripheral nerve injury. However, the role and underlying mechanism of GPNMB in the PNS, especially in peripheral nerve regeneration (PNR), are still unknown and need to be further investigated. In this study, recombinant human GPNMB (rhGPNMB) was injected into a sciatic nerve injury model. It was found that rhGPNMB facilitated the regeneration and functional recovery of the injured sciatic nerve in vivo. Moreover, it was also confirmed that GPNMB activated the Erk1/2 and Akt pathways via binding with Na+/K + -ATPase α1 (NKA α1) and promoted the proliferation and migration of Schwann cells (SCs) and their expression and secretion of neurotrophic factors and neural adhesion molecules in vitro. Our findings demonstrate that GPNMB facilitates PNR through activation of the Erk1/2 and Akt pathways in SCs by binding with NKA α1 and may be a novel strategy for PNR. Glycoprotein non-metastatic melanoma protein B (GPNMB) ubiquitously expressed in central and has neuroprotective effects in central nervous system. In particular, it is also expressed in the peripheral nervous system (PNS) and upregulated after peripheral nerve injury. However, the role and underlying mechanism of GPNMB in the PNS, especially in peripheral nerve regeneration (PNR), is still unknown. This study aimed to in vestigate the role and mechanism of GPNMB in PNR. Here, it was found that rhGPNMB facilitated the regeneration and functional recovery of the injured sciatic nerve in vivo. Moreover, it was confirmed that GPNMB activated the Erk1/2 and Akt pathways via binding with NKA α1 and promoted SCs proliferation and migration and their expression and secretion of neurotrophic factors and neural adhesion molecules. These findings demonstrate that GPNMB facilitates PNR through activation of the Erk1/2 and Akt pathways in SCs via binding with the NKA α1 and may be a novel strategy for PNR. [Display omitted] •GPNMB facilitates regeneration and functional recovery of sciatic nerve.•GPNMB promotes SCs proliferation and migration and their expression and secretion of NTFs and NAMs.•GPNMB activates Erk1/2 and Akt pathways via binding with NKA α1 in SCs.