Functional recovery after peripheral nerve damage is dependent on the reprogramming of differentiated Schwann cells (dSCs) into repair Schwann cells (rSCs), which promotes axonal regeneration and tissue homeostasis. Transition into a repair phenotype requires expression of c-Jun and Sox2, which transcriptionally mediates inhibition of the dSC program of myelination and activates a non-cell-autonomous repair program, characterized by the secretion of neuronal survival and regenerative molecules, formation of a cellular scaffold to guide regenerating axons and activation of an innate immune response. Moreover, rSCs release exosomes that are internalized by peripheral neurons, promoting axonal regeneration. Here, we demonstrate that reprogramming of Schwann cells (SCs) is accompanied by a shift in the capacity of their secreted exosomes to promote neurite growth, which is dependent on the expression of c-Jun (also known as Jun) and Sox2 by rSCs. Furthermore, increased expression of miRNA-21 is responsible for the pro-regenerative capacity of rSC exosomes, which is associated with PTEN downregulation and PI3-kinase activation in neurons. We propose that modification of exosomal cargo constitutes another important feature of the repair program of SCs, contributing to axonal regeneration and functional recovery after nerve injury.

周围神经损伤后的功能恢复取决于分化的雪旺细胞（dSCs）重新编程为修复的雪旺细胞（rSCs），从而促进轴突再生和组织动态平衡。过渡到修复表型需要表达c-Jun和Sox2，它们在转录上介导抑制髓鞘形成的dSC程序并激活非细胞自主的修复程序，其特征是分泌神经元存活和再生分子，形成细胞支架以指导再生轴突和先天免疫反应的激活。此外，rSCs释放被周围神经元内化的外泌体，促进轴突再生。这里，我们证明，雪旺氏细胞（SCs）的重编程伴随着其分泌的外泌体促进神经突生长的能力发生转移，这取决于rSCs对c-Jun（也称为Jun）和Sox2的表达。此外，miRNA-21表达的增加负责rSC外泌体的再生能力，这与神经元中PTEN下调和PI3激酶激活有关。我们建议修改外体货物构成SC修复程序的另一个重要特征，有助于神经损伤后轴突再生和功能恢复。这与神经元中PTEN下调和PI3激酶激活有关。我们建议修改外体货物构成SC修复程序的另一个重要特征，有助于神经损伤后轴突再生和功能恢复。这与神经元中PTEN下调和PI3激酶激活有关。我们建议修改外体货物构成SC修复程序的另一个重要特征，有助于神经损伤后轴突再生和功能恢复。