Effect of Spp1 on nerve degeneration and regeneration after rat sciatic nerve injury

Xingyu Liu,Shusen Cui,Huaiqin Li,Yuhua Sun,Dengbing Yao,Ying Yuan,Meiyuan Li,Yuting Li

doi:10.1186/s12868-017-0348-1

Abstract

BackgroundWallerian degeneration (WD) in injured peripheral nerves is associated with a large number of up- or down-regulated genes, but the effects of these changes are poorly understood. In our previous studies, we reported some key factors that are differentially expressed to activate nerve degeneration and regeneration during WD. Here, we determined the effects of secreted phosphoprotein 1 (Spp1) on WD after rat sciatic nerve injury.ResultsSpp1 was upregulated from 6 h to 14 days after sciatic nerve injury. Altered expression of Spp1 in Schwann cells (SC) resulted in altered mRNA and protein expression levels for cytokines, c-Fos, PKCα and phospho-ERK/ERK and affected SC apoptosis in vitro. Silencing of Spp1 expression in SCs using siRNA technology reduced proliferation and promoted migration of SCs in vitro. By contrast, overexpression of Spp1 promoted proliferation and reduced migration in SCs in vitro. Differential expression of Spp1 after sciatic nerve injury in vivo altered the expression of cytokines, c-Fos, PKCα, and the p-ERK/ERK pathway.ConclusionsSpp1 is a key regulatory factor that affects nerve degeneration and regeneration through c-Fos, PKCα and p-ERK/ERK pathways after rat sciatic nerve injury. These results shed new light on the role of Spp1 in nerve degeneration and regeneration during WD.

Highlights

Wallerian degeneration (WD) in injured peripheral nerves is associated with a large number of up- or down-regulated genes, but the effects of these changes are poorly understood
We previously reported on gene expression signal flow and pathways regulated by key factors as determined by microarray analyses, such as claudins, transforming growth factor beta 1, Secreted phosphoprotein 1 (Spp1), and toll-like receptor 4, during the processes of WD after rat sciatic nerve injury [11,12,13,14,15]
We found that protein levels of c-Fos, PKCα and p-extracelluler regulated protein kinase (ERK)/ERK were significantly changed after transfection of Spp1 small interfering RNA (siRNA) and the pcDNA3.1-Spp1 plasmid (*p < 0.05), indicating that c-Fos, PKCα and p-ERK/ERK signaling pathways could be activated by Spp1 (Fig. 3)

Summary

Introduction

Wallerian degeneration (WD) in injured peripheral nerves is associated with a large number of up- or down-regulated genes, but the effects of these changes are poorly understood. A number of studies have found that nerve injury plays a key role in modulating the activities of Schwann cells and promotes axonal regeneration by releasing a large number of regeneration-related factors, including cytokines, growth factors, and chemokines [5,6,7]. It is Secreted phosphoprotein 1 (Spp1) belongs to the family of secreted acidic proteins. Stimulation of Spp expression leads to an increase in cell pro-inflammatory cytokine levels, the regulatory pathways are not yet known [17,18,19]

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