Neural Regeneration Research ›› 2020, Vol. 15 ›› Issue (4): 739-747.doi: 10.4103/1673-5374.266922

Previous Articles     Next Articles

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).

PDF

144

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