Interleukin‑1β attenuates the proliferation and differentiation of oligodendrocyte precursor cells through regulation of the microRNA‑202‑3p/β‑catenin/Gli1 axis.

Yanhong Li, Lei Liu, Xin Ding, Yong Liu, Qian Yang, Baichen Ren

International journal of molecular medicine 2020 Sep

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The inflammatory cytokine interleukin (IL)‑1β 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‑1β on myelination are poorly understood. Therefore, the present study was designed to investigate whether IL‑1β modifies the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) through regulating the miR‑202‑3p/β‑catenin/glioma‑associated oncogene homolog 1 (Gli1) axis. It was observed that IL‑1β 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‑1β markedly decreased the expression of miR‑202‑3p and increased the protein expression of β‑catenin and Gli1, all of which were reversed by the IL‑1β inhibitor, IL‑1Ra. Treatment with the β‑catenin inhibitor XAV939, Gli1 siRNA, or miR‑202‑3p mimic transfection, attenuated the IL‑1β‑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 β‑catenin and Gli1. As demonstrated by the findings of the present study, IL‑1β suppressed the proliferation and differentiation of OPCs through regulation of the miR‑202‑3p/β‑catenin/Gli1 axis. Therefore, the miR‑202‑3p/β‑catenin/Gli1 axis may be of value as a therapeutic target in multiple sclerosis.

Citation

Yanhong Li, Lei Liu, Xin Ding, Yong Liu, Qian Yang, Baichen Ren. Interleukin‑1β attenuates the proliferation and differentiation of oligodendrocyte precursor cells through regulation of the microRNA‑202‑3p/β‑catenin/Gli1 axis. International journal of molecular medicine. 2020 Sep;46(3):1217-1224