Abstract

BackgroundGrowth factors execute essential biological functions and affect various physiological and pathological processes, including peripheral nerve repair and regeneration. Our previous sequencing data showed that the mRNA coding for betacellulin (Btc), an epidermal growth factor protein family member, was up-regulated in rat sciatic nerve segment after nerve injury, implying the potential involvement of Btc during peripheral nerve regeneration.MethodsExpression of Btc was examined in Schwann cells by immunostaining. The function of Btc in regulating Schwann cells was investigated by transfecting cultured cells with siRNA segment against Btc or treating cells with Btc recombinant protein. The influence of Schwann cell-secreted Btc on neurons was determined using a co-culture assay. The in vivo effects of Btc on Schwann cell migration and axon elongation after rat sciatic nerve injury were further evaluated.ResultsImmunostaining images and ELISA outcomes indicated that Btc was present in and secreted by Schwann cells. Transwell migration and wound healing observations showed that transfection with siRNA against Btc impeded Schwann cell migration while application of exogenous Btc advanced Schwann cell migration. Besides the regulating effect on Schwann cell phenotype, Btc secreted by Schwann cells influenced neuron behavior and increased neurite length. In vivo evidence supported the promoting role of Btc in nerve regeneration after both rat sciatic nerve crush injury and transection injury.ConclusionOur findings demonstrate the essential roles of Btc on Schwann cell migration and axon elongation and imply the potential application of Btc as a regenerative strategy for treating peripheral nerve injury.

Highlights

  • Peripheral nerves exhibited greater regenerative abilities after nerve injury as compared with centralWang et al Mol Med (2021) 27:27Growth factors are natural molecules that function to regulate cellular behaviors

  • Our recent study screened critical growth factors that were differentially expressed after rat sciatic nerve injury by the joint use of high-throughput sequencing data and advanced bioinformatic tools and found that besides these well-investigated growth factors, Btc, a gene encoding for betacellulin (Btc), was robustly up-regulated in the injured sciatic nerve segments (Zhang et al 2019)

  • Btc stimulated Schwann cell migration Isolated and cultured Schwann cells were immunostained with Schwann cell marker S100β to assess cell purity

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Summary

Introduction

Growth factors are natural molecules that function to regulate cellular behaviors Numerous growth factors, such as nerve growth factor, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, and fibroblast growth factors have been identified as essential neurotrophic factors that benefit nerve repair (Gu et al 2011, 2014). Our recent study screened critical growth factors that were differentially expressed after rat sciatic nerve injury by the joint use of high-throughput sequencing data and advanced bioinformatic tools and found that besides these well-investigated growth factors, Btc, a gene encoding for betacellulin (Btc), was robustly up-regulated in the injured sciatic nerve segments (Zhang et al 2019). Our previous sequencing data showed that the mRNA coding for betacellulin (Btc), an epidermal growth factor protein family member, was up-regulated in rat sciatic nerve segment after nerve injury, implying the potential involvement of Btc during peripheral nerve regeneration

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Conclusion

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