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The Regulatory Effect of ERK1 Pathway in the DNA Hypomethylation of MRL/lpr Mice

Received: 17 July 2021     Accepted: 9 August 2021     Published: 18 August 2021
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Abstract

Background: Defective ERK1 activity may regulate the DNA hypomethylation in T cells of lupus mice. Aims: To investigate the function of ERK1 in regulating DNA hypomethylation and explore the potential molecular mechanisms involved in lupus mice. Methods: CD4+T cells were isolated from MRL/lpr and BALB/c mice, activated in vitro in the presence or absence of 5-azacytidine (5-Aza) (a DNA methyltransferase inhibitor)/U0126 (a selective inhibitor of the ERK signaling pathway) respectively. The positive rate of CD4+T cell was measured by flow cytometry, and expression levels of CD70, ERK1, DNA transferase 1 (DNMT1) were estimated by RT-PCR and Western blot. The methylated DNA is detected using the Capture and Detection antibodies, then quantified colorimetrically. Results: The expression level of p-ERK1 in MRL/lpr mice was significantly lower than healthy control (P<0.05); Meanwhile, down regulation of DNMT1 and DNA hypomethylation were found in MRL/lpr mice T cells. In contrary, the expression levels of CD70 increased when compared with healthy control (P<0.05). The same changes were seen in healthy CD4+T cells treated with U0126. Conclusions: DNA hypomethylation regulating mechanisms in lupus T cells were associated with ERK1 signal pathway. U0126 could inhibit ERK1 signal transduction pathway in normal T cells, and induce DNA hypomethylation by regulating the expression of methylation sensitive gene CD70.

Published in International Journal of Immunology (Volume 9, Issue 3)
DOI 10.11648/j.iji.20210903.11
Page(s) 41-46
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This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2021. Published by Science Publishing Group

Keywords

Systemic Lupus Erythematosus, DNA Methylation, ERK1 Signal Pathway, Epigenetics

References
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  • APA Style

    Miaoxuan Luo, Shanshan Wei, Xiangbin Mi, Tangde Zhang, Wu Zhang. (2021). The Regulatory Effect of ERK1 Pathway in the DNA Hypomethylation of MRL/lpr Mice. International Journal of Immunology, 9(3), 41-46. https://doi.org/10.11648/j.iji.20210903.11

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    ACS Style

    Miaoxuan Luo; Shanshan Wei; Xiangbin Mi; Tangde Zhang; Wu Zhang. The Regulatory Effect of ERK1 Pathway in the DNA Hypomethylation of MRL/lpr Mice. Int. J. Immunol. 2021, 9(3), 41-46. doi: 10.11648/j.iji.20210903.11

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    AMA Style

    Miaoxuan Luo, Shanshan Wei, Xiangbin Mi, Tangde Zhang, Wu Zhang. The Regulatory Effect of ERK1 Pathway in the DNA Hypomethylation of MRL/lpr Mice. Int J Immunol. 2021;9(3):41-46. doi: 10.11648/j.iji.20210903.11

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  • @article{10.11648/j.iji.20210903.11,
      author = {Miaoxuan Luo and Shanshan Wei and Xiangbin Mi and Tangde Zhang and Wu Zhang},
      title = {The Regulatory Effect of ERK1 Pathway in the DNA Hypomethylation of MRL/lpr Mice},
      journal = {International Journal of Immunology},
      volume = {9},
      number = {3},
      pages = {41-46},
      doi = {10.11648/j.iji.20210903.11},
      url = {https://doi.org/10.11648/j.iji.20210903.11},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.iji.20210903.11},
      abstract = {Background: Defective ERK1 activity may regulate the DNA hypomethylation in T cells of lupus mice. Aims: To investigate the function of ERK1 in regulating DNA hypomethylation and explore the potential molecular mechanisms involved in lupus mice. Methods: CD4+T cells were isolated from MRL/lpr and BALB/c mice, activated in vitro in the presence or absence of 5-azacytidine (5-Aza) (a DNA methyltransferase inhibitor)/U0126 (a selective inhibitor of the ERK signaling pathway) respectively. The positive rate of CD4+T cell was measured by flow cytometry, and expression levels of CD70, ERK1, DNA transferase 1 (DNMT1) were estimated by RT-PCR and Western blot. The methylated DNA is detected using the Capture and Detection antibodies, then quantified colorimetrically. Results: The expression level of p-ERK1 in MRL/lpr mice was significantly lower than healthy control (PP+T cells treated with U0126. Conclusions: DNA hypomethylation regulating mechanisms in lupus T cells were associated with ERK1 signal pathway. U0126 could inhibit ERK1 signal transduction pathway in normal T cells, and induce DNA hypomethylation by regulating the expression of methylation sensitive gene CD70.},
     year = {2021}
    }
    

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  • TY  - JOUR
    T1  - The Regulatory Effect of ERK1 Pathway in the DNA Hypomethylation of MRL/lpr Mice
    AU  - Miaoxuan Luo
    AU  - Shanshan Wei
    AU  - Xiangbin Mi
    AU  - Tangde Zhang
    AU  - Wu Zhang
    Y1  - 2021/08/18
    PY  - 2021
    N1  - https://doi.org/10.11648/j.iji.20210903.11
    DO  - 10.11648/j.iji.20210903.11
    T2  - International Journal of Immunology
    JF  - International Journal of Immunology
    JO  - International Journal of Immunology
    SP  - 41
    EP  - 46
    PB  - Science Publishing Group
    SN  - 2329-1753
    UR  - https://doi.org/10.11648/j.iji.20210903.11
    AB  - Background: Defective ERK1 activity may regulate the DNA hypomethylation in T cells of lupus mice. Aims: To investigate the function of ERK1 in regulating DNA hypomethylation and explore the potential molecular mechanisms involved in lupus mice. Methods: CD4+T cells were isolated from MRL/lpr and BALB/c mice, activated in vitro in the presence or absence of 5-azacytidine (5-Aza) (a DNA methyltransferase inhibitor)/U0126 (a selective inhibitor of the ERK signaling pathway) respectively. The positive rate of CD4+T cell was measured by flow cytometry, and expression levels of CD70, ERK1, DNA transferase 1 (DNMT1) were estimated by RT-PCR and Western blot. The methylated DNA is detected using the Capture and Detection antibodies, then quantified colorimetrically. Results: The expression level of p-ERK1 in MRL/lpr mice was significantly lower than healthy control (PP+T cells treated with U0126. Conclusions: DNA hypomethylation regulating mechanisms in lupus T cells were associated with ERK1 signal pathway. U0126 could inhibit ERK1 signal transduction pathway in normal T cells, and induce DNA hypomethylation by regulating the expression of methylation sensitive gene CD70.
    VL  - 9
    IS  - 3
    ER  - 

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Author Information
  • Department of Dermatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

  • Department of Dermatology, Zhujiang Hospital, Southern Medical University/The Second School of Clinical Medicine, Guangzhou, China

  • Department of Dermatology, Zhujiang Hospital, Southern Medical University/The Second School of Clinical Medicine, Guangzhou, China

  • Department of Dermatology, Zhujiang Hospital, Southern Medical University/The Second School of Clinical Medicine, Guangzhou, China

  • Department of Dermatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

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