中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (4): 739-747.doi: 10.4103/1673-5374.266922

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

miR-219/miR-338可影响小胶质细胞和星形胶质细胞行为及星形胶质细胞-少突胶质细胞前体细胞的相互作用

  

  • 出版日期:2020-04-15 发布日期:2020-05-29
  • 基金资助:
    新加坡国家研究基金会的NMRC-CBRG资助

Effects of miR-219/miR-338 on microglia and astrocyte behaviors and astrocyte-oligodendrocyte precursor cell interactions

Lan Huong Nguyen1, William Ong1, Kai Wang1, Mingfeng Wang1, Dean Nizetic2, 3, Sing Yian Chew1, 2   

  1. 1 School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, Singapore
    2 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
    3 Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, UK
  • Online:2020-04-15 Published:2020-05-29
  • Contact: Sing Yian Chew, PhD,sychew@ntu.edu.sg.
  • Supported by:
    This work was supported by the Singapore National Research Foundation under its NMRC-CBRG grants (Project award number: NMRC/CBRG/0096/2015) and administered by the Singapore Ministry of Health’s National Medical Research Council and partially supported by the MOE Academic Research Funding (AcRF) Tier 1 grant (RG148/14) and Tier 2 grant (MOE2015-T2-1-023).

摘要:

MiR-219和miR-338是少突胶质细胞特异性微小RNA,其在少突胶质细胞前体细胞中的过表达促进它们分化和成熟为少突胶质细胞,可以增强中枢神经系统损伤后的轴突髓鞘再生。因此,将miR-219/miR-338递送至中枢神经系统可促进少突胶质前体细胞分化、成熟和髓鞘化,从而可用于神经修复。然而,中枢神经系统中的神经损伤还涉及其他细胞类型,例如小胶质细胞和星形胶质细胞。此次体外和体内研究探讨了miR-219/miR-338处理对小胶质细胞和星形胶质细胞的影响。结果发现miR-219/miR-338可减少小胶质细胞促炎细胞因子的表达,并抑制了星形胶质细胞的活化。同时还发现miR-219/miR-338可促进受损星形胶质细胞-少突胶质前体细胞共培养中少突胶质前体细胞的分化和成熟。实验表明miR-219/miR-338可促进中枢神经系统损伤后轴突髓鞘再生。所有动物实验程序均于2016年4月27日和2016年10月8日由南洋理工大学动物护理和使用委员会(IACUC)批准(批准号A0309和A0333)。

orcid: 0000-0002-6084-5967 (Sing Yian Chew)

关键词: 中枢神经系统, 静电, 基因沉默, 神经胶质细胞, 水凝胶, 髓鞘形成, 纳米纤维, 少突胶质细胞, 聚己内酯, 脊髓损伤

Abstract: MiR-219 and miR-338 (miR-219/miR-338) are oligodendrocyte-specific microRNAs. The overexpression of these miRs in oligodendrocyte precursor cells promotes their differentiation and maturation into oligodendrocytes, which may enhance axonal remyelination after nerve injuries in the central nervous system (CNS). As such, the delivery of miR-219/miR-338 to the CNS to promote oligodendrocyte precursor cell differentiation, maturation and myelination could be a promising approach for nerve repair. However, nerve injuries in the CNS also involve other cell types, such as microglia and astrocytes. Herein, we investigated the effects of miR-219/miR-338 treatment on microglia and astrocytes in vitro and in vivo. We found that miR-219/miR-338 diminished microglial expression of pro-inflammatory cytokines and suppressed astrocyte activation. In addition, we showed that miR-219/miR-338 enhanced oligodendrocyte precursor cell differentiation and maturation in a scratch assay paradigm that re-created a nerve injury condition in vitro. Collectively, our results suggest miR-219/miR-338 as a promising treatment for axonal remyelination in the CNS following nerve injuries. All experimental procedures were approved by the Institutional Animal Care and Use Committee (IACUC), Nanyang Technological University (approval No. A0309 and A0333) on April 27, 2016 and October 8, 2016.

Key words: central nervous system, electrospinning, gene silencing, glia, hydrogel, myelination, nanofibers, oligodendroglial, polycaprolactone, spinal cord injury