Betacellulin regulates peripheral nerve regeneration by affecting Schwann cell migration and axon elongation

Molecular Medicine

Yunsong Zhang¹  Fuchao Zhang¹  Sheng Yi¹  Yaxian Wang¹  Wei Liu¹  Qi Shan¹  Feiyu Zhang²  Fengyuan Zhang² 

[1] Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 226001, Nantong, Jiangsu, China;Medical School of Nantong University, 226001, Nantong, Jiangsu, China;

关键词: Peripheral nerve injury;    Betacellulin;    Schwann cell migration;    Axon elongation;    Nerve regeneration;   

DOI  :  10.1186/s10020-021-00292-5

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY