Betacellulin regulates peripheral nerve regeneration by affecting Schwann cell migration and axon elongation.
Betacellulin regulates peripheral nerve regeneration by affecting Schwann cell migration and axon elongation.
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Betacellulin 通过影响雪旺细胞迁移和轴突伸长来调节周围神经再生
DOI：
10.1186/s10020-021-00292-5
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发表时间：
2021-03-25
期刊：
影响因子：
--
通讯作者：
Yi S
中科院分区：
文献类型：
--
作者：
Wang Y;Zhang F;Zhang Y;Shan Q;Liu W;Zhang F;Zhang F;Yi S
研究背景生长因子具有重要的生物学功能，影响周围神经的修复和再生等多种生理和病理过程。我们以前的测序数据表明，β细胞素（BTC），表皮生长因子蛋白家族成员的mRNA编码，上调大鼠坐骨神经节段神经损伤后，暗示BTC在周围神经regeneration.Methodsexpression的雪旺细胞的BTC的表达进行了检查。用Btc重组蛋白处理细胞，用siRNA片段阻断培养细胞，观察Btc对雪旺细胞的调节作用。使用共培养测定来确定雪旺细胞分泌的Btc对神经元的影响。进一步评价Btc对大鼠坐骨神经损伤后雪旺细胞迁移和轴突伸长的体内影响。结果免疫染色图像和ELISA结果表明Btc存在于雪旺细胞中并由雪旺细胞分泌。Transwell迁移和伤口愈合观察显示，转染siRNA抑制Btc的雪旺细胞迁移，而应用外源性Btc促进雪旺细胞迁移。除了对雪旺细胞表型的调节作用外，雪旺细胞分泌的Btc还影响神经元的行为和增加轴突长度。在体内的证据支持的促进作用，BTC在神经再生后，大鼠坐骨神经挤压伤和横断injure.ConclusionOur研究结果表明，必不可少的作用，BTC对雪旺细胞迁移和轴突伸长，并暗示潜在的应用BTC作为一种再生策略，治疗周围神经损伤。
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 againstBtcor 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 againstBtcimpeded 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.
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