The dysregulation of microRNAs in multiple sclerosis and their involvement in the differentiation of oligodendrocyte progenitor cells
(2023)
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- Authors
- Supervisors
- van Pesch, Vincent
- Abstract
- Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disorder of the central nervous system causing neurodegeneration. Its pathogenesis is incompletely understood. microRNAs conceivably affect the fate of the involved cells by posttranscriptional regulation. We identified 21 microRNAs dysregulated in the cerebrospinal fluid, serum and/or peripheral blood mononuclear cells (PBMCs) of relapsing/remitting MS patients and evidenced that the dysregulation of 13 microRNAs in PBMCs of a second cohort was rather driven by inactive MS and barely affected by treatment. Certain microRNAs also correlated with IL21/FOXP3 expression. We further evidenced that several microRNAs affect the differentiation of oligodendrocyte progenitor cells (OPC), key to remyelination. Hereby miR-33-3p, miR-34c-5p and miR-124-5p arrest OPC differentiation at a late progenitor stage, miR-145-5p at a premyelinating stage, while miR-214-3p promotes OPC differentiation into mature oligodendrocytes. We propose promising mRNA targets and pathways by which they could do so. These could unravel new mechanisms of MS pathogenesis and potential therapeutic targets.
- Affiliations
Citations
Perdaens, O. (2023). The dysregulation of microRNAs in multiple sclerosis and their involvement in the differentiation of oligodendrocyte progenitor cells. https://hdl.handle.net/2078.5/233795