Interleukin-1 Beta Attenuates The Proliferation And Differentiation Of Oligodendrocyte Precursor Cells Through Regulation Of The Microrna-202-3p/Beta-Catenin/Gli1 Axis

The inflammatory cytokine interleukin (IL)-1 beta has been implicated in demyelinating diseases, such as multiple sclerosis and experimental autoimmune encephalomyelitis, and brain degenerative diseases, such as Alzheimer's disease. However, the cellular and molecular mechanisms underlying the damaging effects of IL-1 beta on myelination are poorly understood. Therefore, the present study was designed to investigate whether IL-1 beta modifies the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) through regulating the miR-202-3p/beta-catenin/glioma-associated oncogene homolog 1 (Gli1) axis. It was observed that IL-1 beta significantly attenuated the proliferation and differentiation of OPCs, as evidenced by a decrease in bromodeoxyuridine incorporation and reduced percentage of myelin basic protein-positive cells among the total number of oligodendrocyte transcription factor 2-positive cells. In addition, IL-1 beta markedly decreased the expression of miR-202-3p and increased the protein expression of beta-catenin and Gli1, all of which were reversed by the IL-1 beta inhibitor, IL-1Ra. Treatment with the beta-catenin inhibitor XAV939, Gli1 siRNA, or miR-202-3p mimic transfection, attenuated the IL-1 beta-induced suppression of OPC proliferation and differentiation. Treatment with XAV939 decreased the expression of Gli1. Transfection of miR-202-3p mimic attenuated the expression of beta-catenin and Gli1. As demonstrated by the findings of the present study, IL-1 beta suppressed the proliferation and differentiation of OPCs through regulation of the miR-202-3p/beta-catenin/Gli1 axis. Therefore, the miR-202-3p/ beta-catenin/Gli1 axis may be of value as a therapeutic target in multiple sclerosis.