Oridonin enhances γ‑globin expression in erythroid precursors from patients with β‑thalassemia via activation of p38 MAPK signaling

  • Authors:
    • Lishan Guo
    • Jia Chen
    • Qianying Wang
    • Junliang Zhang
    • Weimin Huang
  • View Affiliations

  • Published online on: November 25, 2019     https://doi.org/10.3892/mmr.2019.10848
  • Pages: 909-917
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Abstract

Upregulation of fetal hemoglobin expression can alleviate the severity of β‑thalassaemia. This study aimed to investigate the effects of Oridonin (ORI, a diterpenoid compound) on γ‑globin expression in human erythroid precursor cells and the potential underlying mechanisms. Erythroid precursor cells were enriched from 12 patients with β‑thalassaemia by two‑phase culture. The cells were then treated with different doses of ORI and the survival of erythroid precursor cells was determined. In addition, the expression levels of γ‑globin and potential mechanisms were analyzed by reverse transcription‑quantitative PCR, western blotting and chromatin immunoprecipitation. Treatment with 0.5 µM ORI preferably enhanced γ‑globin expression and exhibited little cytotoxicity. Similar to sodium butyrate (NaB, a histone deacetylase inhibitor), ORI significantly increased p38 mitogen‑activated protein kinase (MAPK) activation, γ‑globin expression, histone H3 and H4 acetylation at the Gγ‑ and Aγ‑globin promoters, and cAMP‑response element binding protein 1 (CREB1) phosphorylation. These effects were significantly mitigated by treatment with SB23580, a p38 MAPK inhibitor, in erythroid precursor cells. Therefore, ORI may effectively enhance γ‑globin expression by activating p38 MAPK and CREB1, leading to histone modification in γ‑globin gene promoters during the maturation of erythroid precursor cells. These findings suggested that ORI may be a novel and potential therapeutic agent for the treatment of β‑thalassaemia.
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February 2020
Volume 21 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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APA
Guo, L., Chen, J., Wang, Q., Zhang, J., & Huang, W. (2020). Oridonin enhances γ‑globin expression in erythroid precursors from patients with β‑thalassemia via activation of p38 MAPK signaling. Molecular Medicine Reports, 21, 909-917. https://doi.org/10.3892/mmr.2019.10848
MLA
Guo, L., Chen, J., Wang, Q., Zhang, J., Huang, W."Oridonin enhances γ‑globin expression in erythroid precursors from patients with β‑thalassemia via activation of p38 MAPK signaling". Molecular Medicine Reports 21.2 (2020): 909-917.
Chicago
Guo, L., Chen, J., Wang, Q., Zhang, J., Huang, W."Oridonin enhances γ‑globin expression in erythroid precursors from patients with β‑thalassemia via activation of p38 MAPK signaling". Molecular Medicine Reports 21, no. 2 (2020): 909-917. https://doi.org/10.3892/mmr.2019.10848