Toll-Like Receptor 4 (TLR4) Expression Affects Schwann Cell Behavior in vitro

Huanhuan Zhang,Chunwang Zhang,Dengbing Yao,Yun Zhu,Rui Hou,Zhiwei Shao,Zhihao Li,Lingyu Shi

doi:10.1038/s41598-018-28516-5

Abstract

Peripheral nerve injury can result in the decreased quality of life and bring us economic burden on society and individuals. Wallerian degeneration (WD) is critical for nerve degeneration and regeneration, but the mechanisms of WD are still elusive. Here, we report the effect of Toll-like receptor 4 (TLR4) on cultured Schwann cells (SCs) in vitro. The data showed that TLR4 expression was up-regulated after sciatic nerve injury of rat. TLR4 was expressed in cultured SCs. Enhanced or silenced expression of TLR4 affected SC proliferation, migration, apoptosis and relative gene expression. Furthermore, altered expression of TLR4 resulted in expression changes in c-Jun, ERK and catenin but not AKT and c-Fos pathways in SCs. These results suggested that TLR4 may be an important effective target in peripheral nerve degeneration and/or regeneration during WD in future investigations.

Highlights

In our previous study, we reported on the presence of gene expression pathways and signal flow regulated by key factors, such as claudins, transforming growth factor, beta 1 (TGF-β1), secreted phosphoprotein 1 (SPP1), Toll-like receptors (TLRs), and Fas Ligand Gene (Faslg), during Wallerian degeneration (WD) in nerve stumps after sciatic nerve injury in the rat using microarray analysis[7,8,9,10,11]
Toll-like receptor 4 (TLR4) and S100B were colocalized in Schwann cells (SCs), indicating that TLR4 is expressed in the rat sciatic nerve (Fig. 1)
The results revealed that the TLR4 expression level was increased from 1 to 4 weeks after injury

Summary

Introduction

We reported on the presence of gene expression pathways and signal flow regulated by key factors, such as claudins, transforming growth factor, beta 1 (TGF-β1), secreted phosphoprotein 1 (SPP1), Toll-like receptors (TLRs), and Fas Ligand Gene (Faslg), during WD in nerve stumps after sciatic nerve injury in the rat using microarray analysis[7,8,9,10,11]. We reported the role of TLR4 on cell migration and proliferation, cell apoptosis, and signal pathways in Schwann cells in vitro. TLR4 is expressed in neurons and central nervous system cells, including astrocytes and microglia. It is involved in nervous system development and regulates the differentiation and proliferation of adult neuronal precursor cells. Loss of TLR4 function showed that nerve injury induced behavioral hypersensitivity. Our study will help us to better understand the response of TLR4 to WD and outline the mechanisms by which WD regulates nerve injury and regeneration. We explored the functions of TLR4 on cell migration and proliferation, cell apoptosis, and signal pathways in cultured SCs in vitro

Methods

Results

Conclusion