Interleukin-1β Promotes Schwann Cells De-Differentiation in Wallerian Degeneration via the c-JUN/AP-1 Pathway.

Gang Chen,Wenjin Wang,Wei Wang,Yimei Wang,Xiaohe Luo,Fei Zhu

doi:10.3389/fncel.2019.00304

Abstract

Schwann cells (SCs) de-differentiate in Wallerian degeneration (WD) following nerve injury and, by doing so, can actively promote nerve repair and functional recovery. An innate-immune response is an important component of the complex of events referred to as WD. Damaged peripheral nervous system SCs produce IL-1β and other inflammatory cytokines. We hypothesized that, in addition to a role in immune responses, IL-1β participates in de-differentiation and proliferation of SCs. qPCR and ELISA demonstrated that expression of IL-1β mRNAs and protein increased after nerve injury. Immunofluorescent staining and western blotting demonstrated that expression of the p75 neurotrophin receptor (p75NTR) was significantly increased and levels of myelin protein zero (MPZ) were significantly decreased after IL-1β exposure compared with control groups in vitro WD. Additionally, qPCR demonstrated that IL-1β elevated expression of the de-differentiation gene p75NTR and decreased expression of myelination locus MPZ and promoted SCs de-differentiation. Furthermore, immunofluorescent staining, western blotting, qPCR and ELISA revealed that IL-1β promoted c-JUN expression and activation of AP-1 activity of SCs in an in vitro WD model. Finally, Immunofluorescent staining illustrated that IL-1β elevated expression of Ki67 in SCs nuclei, the apoptosis of SCs were detected by TUNEL. SCs of WD produce IL-1β which promotes SCs de-differentiation and proliferation.

Highlights

The ultimate goal of regenerative medicine research is to enable replacement of lost or damaged tissues or organs
Relative quantification of IL-1β mRNA was performed by qPCR, and results were analyzed by one-way ANOVA followed by Least Significant Difference (LSD) test (Figure 1A)
The analysis revealed expression of IL-1β mRNA by Schwann cells (SCs) increased after sciatic nerves (SNs) injury, peaking at 12 h

Summary

INTRODUCTION

The ultimate goal of regenerative medicine research is to enable replacement of lost or damaged tissues or organs. Following de-differentiation, SCs clear myelin debris by autophagy, in addition, SCs contribute to macrophage-mediated myelin removal and re-enter the cell cycle, proliferate, and form bands of Büngner, which support and direct outgrowing axons to sites of innervation (Martini et al, 2008; Rotshenker, 2011; Brosius et al, 2017) These cells express and secrete a large number of axonal growth promoting factors, re-differentiate and myelinate regenerated axons, which eventually leads to substantial functional recovery (WoszczyckaKorczynska et al, 2013; Jessen and Mirsky, 2016). Damaged SCs may induce cell apoptosis and limit functional recovery of peripheral nerves (Zhao et al, 2017) This sequence emphasizes the central function of SC de-differentiation in PNS regeneration. Nerve segments were extracted in 1 ml PBS containing a mixture of protease inhibitors (Roche Molecular Biochemicals)

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RESULTS

DISCUSSION

CONCLUSION

ETHICS STATEMENT