論文 - 詳細
| RRC ID | 77297 |
|---|---|
| 著者 | Sun Y, Habara A, Le CQ, Nguyen N, Chen R, Murphy GJ, Chui DHK, Steinberg MH, Cui S. |
| タイトル | Pharmacologic induction of PGC-1α stimulates fetal haemoglobin gene expression. |
| ジャーナル | Br J Haematol |
| Abstract |
Sickle cell disease (SCD) is a genetic disorder that affects millions around the world. Enhancement of fetal γ-globin levels and fetal haemoglobin (HbF) production in SCD patients leads to diminished severity of many clinical features of the disease. We recently identified the transcriptional co-activator PGC-1α as a new protein involved in the regulation of the globin genes. Here, we report that upregulation of PGC-1α by infection with a lentivirus expressing PGC-1α or by the small-molecule PGC-1α agonist ZLN005 in human primary erythroid progenitor CD34+ cells induces both fetal γ-globin mRNA and protein expression as well as the percentage of HbF-positive cell (F cells) without significantly affecting cell proliferation and differentiation. We further found that the combination of ZLN005 and hydroxyurea (hydroxycarbamide) exhibited an additive effect on the expression of γ-globin and the generation of F cells from cultured CD34+ cells. In addition, ZLN005 induced robust expression of the murine embryonic βh1-globin gene and to a lesser extent, human γ-globin gene expression in sickle mice. These findings suggest that activation of PGC-1α by ZLN005 might provide a new path for modulating HbF levels with potential therapeutic benefit in β-hemoglobinopathies. |
| 巻・号 | 197(1) |
| ページ | 97-109 |
| 公開日 | 2022-4-1 |
| DOI | 10.1111/bjh.18042 |
| PMID | 35118652 |
| MeSH | Anemia, Sickle Cell* / drug therapy Anemia, Sickle Cell* / genetics Animals Fetal Hemoglobin / metabolism Gene Expression Gene Expression Regulation Hemoglobinopathies* Humans Mice Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism* gamma-Globins / genetics |
| IF | 5.518 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HUDEP-1(RCB4556) HUDEP-2(RCB4557) |