Peripheral nerve injury (PNI) is encountered relatively commonly in the clinic and often results in long-term functional deficits. Research to develop methods to improve regeneration following nerve injury is ongoing. Numerous studies have shown that adipose-derived stem cells (ADSCs) promote the regeneration of peripheral nerve injury; however, the mechanism is unclear. Autophagy, a highly conserved intracellular process responsible for maintaining cellular homeostasis, and Schwann cells (SCs), play important roles in regeneration after PNI. In the present study, we explored the effect and mechanism of exosomes produced by adipose-derived stem cells (ADSC-Exos) on autophagy of SCs in PNI, as well as their effect on the regeneration of the nerve myelin sheath. The levels of autophagy and the expression of karyopherin subunit alpha 2 (Kpna2) in SCs increased markedly after the sciatic nerve was injured in SCs (SNI-SCs). The enhanced autophagy and the upregulated Kpna2 in SNI-SCs were inhibited after treatment with ADSC-Exos in vivo and in vitro. The effect of ADSC-Exos on inhibiting SC autophagy was blocked by overexpression of Kpna2 in SNI-SCs. Using quantitative real-time reverse transcription PCR, ADSC-Exos were demonstrated to contain a large amount of miRNA-26b, which was predicted to regulate Kpna2 on the TargetScan website. The effect of ADSC-Exos on inhibiting SCs autophagy was blocked after the silencing of miRNA-26b. Moreover, ADSC-Exos promoted the regeneration of the myelin sheath by inhibiting SC autophagy in rat SNI models. In conclusion, our results indicated that ADSC-Exos promote the regeneration of the myelin sheath by moderately reducing autophagy of injured SCs via miRNA-26b downregulation of Kpna2.

周围神经损伤（PNI）在临床中相对常见，通常会导致长期功能缺陷。开发改善神经损伤后再生方法的研究正在进行中。大量研究表明，脂肪源性干细胞（ADSC）可促进周围神经损伤的再生；然而，其机制尚不清楚。自噬是一种高度保守的细胞内过程，负责维持细胞稳态，而雪旺细胞 (SC) 在 PNI 后的再生中发挥着重要作用。在本研究中，我们探讨了脂肪源性干细胞（ADSC-Exos）产生的外泌体对PNI中SCs自噬的影响和机制，以及它们对神经髓鞘再生的影响。坐骨神经损伤后SCs（SNI-SCs）自噬水平和核转运蛋白α2亚基（ Kpna2 ）表达显着增加。在体内和体外用 ADSC-Exos 处理后，SNI-SCs 中增强的自噬和上调的Kpna2均受到抑制。 ADSC-Exos 抑制 SC 自噬的作用被 SNI-SC 中Kpna2的过表达所阻断。使用定量实时逆转录PCR，ADSC-Exos被证明含有大量的miRNA-26b，TargetScan网站上预测该miRNA-26b可以调节Kpna2 。沉默 miRNA-26b 后，ADSC-Exos 抑制 SCs 自噬的作用被阻断。此外，ADSC-Exos 通过抑制大鼠 SNI 模型中的 SC 自噬来促进髓鞘再生。 总之，我们的结果表明，ADSC-Exos通过miRNA-26b 下调Kpna2适度减少受损 SC 的自噬，从而促进髓鞘再生。