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Role and Mechanism of Ozanimod (RPC1063) in Oligodendrocyte Precursor Cell Differentiation |
ZHANG Ying1,2,KONG Xiang-xi2,HOU Lin1,WANG Shu-kun2,**(),YUAN Zeng-qiang1,2,**() |
1 School of Basic Medicine, Qingdao University, Qingdao 266071, China 2 Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Beijing 100850, China |
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Abstract Objective: This study aims to pinpoint the role of Ozanimod (RPC1063) in the differentiation of oligodendrocyte precursor cell (OPC) and investigate the underlying molecular mechanism.Methods: OPC was directly isolated by immune adsorption and indentified through immunofluorescence and quantitative real time-PCR. Firstly, the mRNA level of S1pr family genes was detected by qRT-PCR during the cerebral cortex development and OPC differentiation. Then, viability of OPC treated with different concentrations of RPC1063 was measured by MTT assay and ATP cell viability assay. Moreover, by means of immunofluorescence, qRT-PCR, and Western blot, we analysed the effects of RPC1063 on the differentiation rate of OPC, and the mRNA or protein level of OPC-differentiation associated genes.Results: High purity of OPC could be obtained by the method of immune adsorption from the cortex of mice. There was no significant effect of RPC1063 on cell viability at concentrations of 0, 0.1, 1, 5, 50, 100nmol/L. Additionally, up-regulation of O4+ or MBP+ cells, and protein level of MBP and mRNA level of Mbp, Sox10, Cnp, or Plp were observed in OPC treated with RPC1063. Moreover, in RPC1063-treated Oli-neu cells, the protein levels of pAKT, p-mTOR and p-4EBP1 were significantly increased at 5min. Besides, the proteins related to p-AKT-mTOR signaling pathway were also significantly increased in OPC. The promotion of RPC1063 on OPC differentiation was weakened by the inhibition of mTOR pathway.Conclusion: RPC1063 promotes the differentiation of oligodendrocyte precursor cell through activating the AKT-mTOR signaling pathway.
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Received: 14 December 2019
Published: 23 June 2020
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Corresponding Authors:
Shu-kun WANG,Zeng-qiang YUAN
E-mail: wangshukun954215@163.com;zqyuan@bmi.ac.cn
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