中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (4): 714-720.doi: 10.4103/1673-5374.295342

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

下调窖蛋白1表达可促进人脂肪间充质干细胞向多巴胺能神经元样分化

  

  • 出版日期:2021-04-15 发布日期:2020-12-21
  • 基金资助:
    国家干细胞临床研究注册项目(CMR-20161129-1003);大连市科技创新基金项目(2018J11CY025)

Caveolin-1 downregulation promotes the dopaminergic neuron-like differentiation of human adipose-derived mesenchymal stem cells

Chao Han1, 2, #, Ya-Jun Wang3, #, Ya-Chen Wang1, 2, Xin Guan1, 4, Liang Wang1, 4, Li-Ming Shen1, 4, Wei Zou3, Jing Liu1, 2, 4, *#br#   

  1. 1 Stem Cell Clinical Research Center, Regenerative Medicine Center, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China;  2 National Joint Engineering Laboratory, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China;  3 College of Life Science, Liaoning Normal University, Dalian, Liaoning Province, China;  4 Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, Liaoning Province, China
  • Online:2021-04-15 Published:2020-12-21
  • Contact: Jing Liu, PhD, liujing.dlrmc@hotmail.com.
  • Supported by:
    This work was supported by National Stem Cell Clinical Research Registered Project, No. CMR-20161129-1003 (to JL); Dalian Science and Technology Innovation Fund, No. 2018J11CY025 (to JL).

摘要:

已有研究显示,窖蛋白1参与调节间充质干细胞的分化,但然而其在人脂肪间充质干细胞分化为类多巴胺能神经元细胞中的作用仍不清楚。实验旨在观察窖蛋白1是否可以调节人脂肪间充质干细胞向类多巴胺能神经元的分化?通过RNA干扰技术下调节窖蛋白1表达是否能够促进人脂肪间充质干细胞分化为类多巴胺能神经元细胞?(1)通过检测形态学及相关标记蛋白酪氨酸羟化酶、Lmx1a及Nurr1的基因表达情况,评估人脂肪间充质干细胞分化为多巴胺能神经元的效率;(2)基因及蛋白检测结果显示,在人脂肪间充质干细胞向类多巴胺能神经元的分化过程中窖蛋白1表达减少,下调窖蛋白1表达能够促进人脂肪间充质干细胞向类多巴胺能神经元分化,而且可提高细胞中酪氨酸羟化酶、Lmx1a及Nurr1的表达;(2) 因此推断,窖蛋白1在干细胞向多巴胺能神经元分化中起负向调控作用,可能是分化信号通路中一个潜在的靶向调控分子。

https://orcid.org/0000-0002-0493-296X (Jing Liu)

关键词: 帕金森病, 体外, 可塑性, 细胞, 神经分化, 干细胞, 蛋白质, 因子

Abstract: Previous studies have shown that caveolin-1 is involved in regulating the differentiation of mesenchymal stem cells. However, its role in the differentiation of human adipose mesenchymal stem cells into dopaminergic neurons remains unclear. The aim of this study was to investigate whether caveolin-1 regulates the differentiation of human adipose mesenchymal stem cells into dopaminergic-like neurons. We also examined whether the expression of caveolin-1 could be modulated by RNA interference technology to promote the differentiation of human adipose mesenchymal stem cells into dopaminergic-like neurons. The differentiation of human adipose mesenchymal stem cells into dopaminergic neurons was evaluated morphologically and by examining expression of the markers tyrosine hydroxylase, Lmx1a and Nurr1. The analyses revealed that during the differentiation of human adipose mesenchymal stem cells into dopaminergic neurons, the expression of caveolin-1 is decreased. Notably, the downregulation of caveolin-1 promoted the differentiation of human adipose mesenchymal stem cells into dopaminergic-like neurons, and it increased the expression of tyrosine hydroxylase, Lmx1a and Nurr1. Together, our findings suggest that caveolin-1 plays a negative regulatory role in the differentiation of dopaminergic-like neurons from stem cells, and it may therefore be a potential molecular target for strategies for regulating the differentiation of these cells. This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Dalian Medical University of China (approval No. PJ-KS-KY-2020-54) on March 7, 2017.

Key words: cells, factor, in vitro, neural differentiation, Parkinson’s disease, plasticity, protein, stem cells