Exosomes produced by adipose-derived stem cells inhibit schwann cells autophagy and promote the regeneration of the myelin sheath
Exosomes produced by adipose-derived stem cells inhibit schwann cells autophagy and promote the regeneration of the myelin sheath
复制标题
脂肪干细胞产生的外泌体抑制雪旺细胞自噬并促进髓鞘再生。
DOI：
10.1016/j.biocel.2021.105921
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发表时间：
2021-01-12
影响因子：
4
通讯作者：
Lin，Haodong
中科院分区：
文献类型：
--
作者：
Yin，Gang;Yu，Bing;Lin，Haodong
周围神经损伤（PNI）是临床上比较常见的一种损伤，常导致长期的功能障碍。开发改善神经损伤后再生的方法的研究正在进行中。大量研究表明，脂肪干细胞（ADSCs）促进周围神经损伤的再生，但具体机制尚不清楚。自噬是一种高度保守的细胞内过程，负责维持细胞内稳态，雪旺细胞（SC）在PNI后的再生中发挥重要作用。本研究探讨脂肪干细胞产生的exosomes（ADSC-Exos）对PNI中SC自噬的影响及其机制，以及对神经髓鞘再生的影响。坐骨神经损伤后，神经干细胞（SNI-SCs）自噬水平和Kpna 2表达明显增加。ADSC-Exosin在体内和体外均能抑制SNI-SCs增强的自噬和上调的Kpna 2。ADSC-Exos抑制SC自噬的作用可被SNI-SC中Kpna 2的过表达所阻断。利用实时定量逆转录PCR，ADSC-Exos被证明含有大量的miRNA-26 b，其在TargetScan网站上被预测为调节Kpna 2。ADSC-Exos抑制SC自噬的作用在miRNA-26 b沉默后被阻断。此外，ADSC-Exos通过抑制大鼠SNI模型中的SC自噬来促进髓鞘的再生。总之，我们的结果表明，ADSC-Exos通过适度减少受损SCsmiRNA-26 b下调Kpna 2的自噬来促进髓鞘的再生。
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 upregulatedKpna2in SNI-SCs were inhibited after treatment with ADSC-Exosin vivoandin vitro. The effect of ADSC-Exos on inhibiting SC autophagy was blocked by overexpression ofKpna2in 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 regulateKpna2on 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 SCsviamiRNA-26b downregulation ofKpna2.