中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (6): 1357-1363.doi: 10.4103/1673-5374.327353

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

皮肤源性前体细胞分化的许旺细胞旁分泌途径抑制自噬

  

  • 出版日期:2022-06-15 发布日期:2021-12-17

Schwann cells differentiated from skin-derived precursors provide neuroprotection via autophagy inhibition in a cellular model of Parkinson’s disease

Jia-Nan Yan1, 2, #, Hai-Ying Zhang1, 2, #, Jun-Rui Li3, Ying Chen1, 4, Yong-Cheng Jiang1, 2, Jia-Bing Shen1, 2, Kai-Fu Ke1, *, Xiao-Su Gu1, *   

  1. 1Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China; 2Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China; 3Department of Clinical Medicine, The First Clinical Medical College of Xuzhou Medical University, Xuzhou, Jiangsu Province, China; 4Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Afflicted Hospital of Soochow University, Suzhou, Jiangsu Province, China
  • Online:2022-06-15 Published:2021-12-17
  • Contact: Xiao-Su Gu, MD, Guxiaosu001@163.com; Kai-Fu Ke, MD, kekaifu_nt@126.com.
  • Supported by:
    This study was supported by Technology Project of Nantong of China, Nos. JC2020052 (to XSG), JCZ19087 (to XSG); and the National Natural Science Foundation of China, Nos. 81873742 (to KFK), 81901195 (to JBS), 81502867 (to TX), 82073627 (to TX). 

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摘要：

有研究显示，细胞自噬在帕金森病中起重要作用。为此，实验设计假设皮肤源性前体细胞可通过影响自噬产生神经保护作用。此次实验将皮肤源性前体细胞分化的许旺细胞的培养基用于预处理6-羟基多巴胺损伤的SH-SY5Y细胞。结果显示：（1）皮肤源性前体细胞分化的许旺细胞的培养基可明显增强6-羟基多巴胺损伤的SH-SY5Y细胞的活性，减少过度自噬，增加细胞中酪氨酸羟化酶表达，并降低α-突触核蛋白表达以及自噬体数量，同时活化了PI3K/AKT/mTOR 通路。（2）自噬激活剂雷帕霉素可抑制皮肤源性前体细胞分化的许旺细胞的培养基的作用；自噬抑制剂3-甲基腺嘌呤则作用相反。（3）实验结果证实了皮肤源性前体细胞分化的许旺细胞，可通过旁分泌作用影响PI3K/AKT/mTOR通路抑制自噬，从而发挥了神经保护作用。动物实验于2018年10月9日经南通大学实验动物中心动物伦理委员会批准（批准号S20181009-205）。

https://orcid.org/0000-0002-3064-956X (Xiao-Su Gu)

关键词: 皮肤源性前体细胞分化而来的许旺细胞, 自噬, α-突触核蛋白, 自噬体, 神经保护, 帕金森病, PI3K/AKT/mTOR通路, 神经再生

Abstract: Autophagy has been shown to play an important role in Parkinson’s disease. We hypothesized that skin-derived precursor cells exhibit neuroprotective effects in Parkinson’s disease through affecting autophagy. In this study, 6-hydroxydopamine-damaged SH-SY5Y cells were pretreated with a culture medium containing skin-derived precursors differentiated into Schwann cells (SKP-SCs). The results showed that the SKP-SC culture medium remarkably enhanced the activity of SH-SY5Y cells damaged by 6-hydroxydopamine, reduced excessive autophagy, increased tyrosine hydroxylase expression, reduced α-synuclein expression, reduced the autophagosome number, and activated the PI3K/AKT/mTOR pathway. Autophagy activator rapamycin inhibited the effects of SKP-SCs, and autophagy inhibitor 3-methyladenine had the opposite effect. These findings confirm that SKP-SCs modulate the PI3K/AKT/mTOR pathway to inhibit autophagy, thereby exhibiting a neuroprotective effect in a cellular model of Parkinson’s disease. This study was approved by the Animal Ethics Committee of Laboratory Animal Center of Nantong University (approval No. S20181009-205) on October 9, 2018.

Key words: alpha-synuclein, autophagosomes, autophagy, neural regeneration, neuroprotection, Parkinson’s disease, PI3K/AKT/mTOR pathway, skin-derived precursor Schwann cells

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