Plastrum testudinis induces γ-globin gene expression through epigenetic histone modifications within the γ-globin gene promoter via activation of the p38 MAPK signaling pathway

  • Authors:
    • Xinhua Qian
    • Jia Chen
    • Danhua Zhao
    • Lishan Guo
    • Xinlai Qian
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  • Published online on: April 8, 2013     https://doi.org/10.3892/ijmm.2013.1338
  • Pages: 1418-1428
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Abstract

The pharmacologically-induced expression of the γ-globin gene, to increase fetal hemoglobin (HbF) production, is a therapeutic strategy used for the treatment of β-thalassemia and sickle cell anemia (SCA). The aim of this study was to investigate the effects of Plastrum testudinis (PT) on differentiation, proliferation, γ-globin gene expression and HbF synthesis in human erythroid cells. For this purpose, we used the K562 human leukemia cell line and human erythroid progenitor cells from normal donors and patients with β-thalassemia cultured using the two-phase liquid culture system. The effects of PT on erythroid differentiation, proli­feration, γ-globin gene expression and HbF synthesis, as well as the involvement of epigenetic histone modifications within the γ-globin gene promoter via activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway, were assessed by benzidine staining, trypan-blue dye exclusion, quantitative real-time RT-PCR (qRT-PCR), western blot analysis and chromatin immunoprecipitation (ChIP). PT promoted the erythroid differentiation of K562 cells, and increased γ-globin mRNA accumulation and HbF synthesis without inhibiting cell proliferation in K562 cells and human erythroid progenitors. PT exerted no effect on α- and β-globin gene expression. In human erythroid cells, PT activated the p38 MAPK signaling pathway, and enhanced the acetylation of histone H3 and H4, the phosphorylation of histone H3 within the Gγ- and Aγ-globin gene promoter regions, γ-globin mRNA accumulation and HbF synthesis. These effects were suppressed by pre-treatment with the p38 MAPK inhibitor, SB203580. Epigenetic histone modifications within γ-globin gene promoter regions, via activation of the p38 MAPK signaling pathway, are important for the induction of γ-globin gene expression in human erythroid cells by PT. PT may be a novel potential therapeutic agent for β-hemoglobinopathies, including β-thalassemia and SCA.
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June 2013
Volume 31 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Qian X, Chen J, Zhao D, Guo L and Qian X: Plastrum testudinis induces γ-globin gene expression through epigenetic histone modifications within the γ-globin gene promoter via activation of the p38 MAPK signaling pathway. Int J Mol Med 31: 1418-1428, 2013.
APA
Qian, X., Chen, J., Zhao, D., Guo, L., & Qian, X. (2013). Plastrum testudinis induces γ-globin gene expression through epigenetic histone modifications within the γ-globin gene promoter via activation of the p38 MAPK signaling pathway. International Journal of Molecular Medicine, 31, 1418-1428. https://doi.org/10.3892/ijmm.2013.1338
MLA
Qian, X., Chen, J., Zhao, D., Guo, L., Qian, X."Plastrum testudinis induces γ-globin gene expression through epigenetic histone modifications within the γ-globin gene promoter via activation of the p38 MAPK signaling pathway". International Journal of Molecular Medicine 31.6 (2013): 1418-1428.
Chicago
Qian, X., Chen, J., Zhao, D., Guo, L., Qian, X."Plastrum testudinis induces γ-globin gene expression through epigenetic histone modifications within the γ-globin gene promoter via activation of the p38 MAPK signaling pathway". International Journal of Molecular Medicine 31, no. 6 (2013): 1418-1428. https://doi.org/10.3892/ijmm.2013.1338