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

Guo,Lishan; Chen,Jia; Wang,Qianying; Zhang,Junliang; Huang,Weimin

doi:10.3892/mmr.2019.10848

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
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Affiliations: Department of Neonatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Neonatology, Pediatric Clinics of Guangdong Women and Children Hospital, Guangzhou, Guangdong 510000, P.R. China, Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
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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