Lineage restriction of the RARα gene expression in myeloid differentiation
Lineage restriction of the RARα gene expression in myeloid differentiation
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DOI：
10.1182/blood.v98.8.2563
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发表时间：
2001-10
期刊：
影响因子：
20.3
通讯作者：
Jun Zhu;C. Heyworth;A. Glasow;Qiuhua Huang;K. Petrie;M. Lanotte;G. Benoit;R. Gallagher;S. Waxman;T. Enver;A. Zelent
中科院分区：
文献类型：
--
作者：
Jun Zhu;C. Heyworth;A. Glasow;Qiuhua Huang;K. Petrie;M. Lanotte;G. Benoit;R. Gallagher;S. Waxman;T. Enver;A. Zelent
为了更好地了解类维生素A在骨髓生成中的作用，在因子依赖性细胞Paterson (FDCP)-mixA4小鼠祖细胞分化过程中检测了类维生素A受体基因（视黄酸受体[RAR]和类维生素A X受体[RXR]）的表达。未分化 A4 细胞中表达的主要受体是 RARα（主要是 RARα1 亚型）。用粒细胞和粒细胞-巨噬细胞集落刺激因子诱导骨髓单核细胞分化后，RARα 表达（特别是 RARα2 亚型）显着增加。相反，两种 RARα 亚型的表达在用促红细胞生成素 (EPO) 诱导红系分化后迅速消失。观察到 RXRα 表达的适度诱导，特别是在骨髓单核细胞谱系的分化过程中。无论分化途径如何，RARγ2 和 RXRβ 的低表达水平保持不变。与基因表达模式一致，RARα 激动剂和拮抗剂分别刺激 FDCP-mixA4 细胞的骨髓单核细胞和红细胞分化。综上所述，这些结果表明，红细胞生成和粒细胞生成分别需要减少和增强 RARα 活性，这在生理全反式视黄酸 (RA) 浓度下可以通过 EPO 和骨髓单核细胞生长因子对其表达的相互影响来实现。这一假设得到了数据的证实，数据显示，RA 正向调节 RARα2 的表达，可以对红细胞分化产生抑制作用。
To better understand the role of retinoids in myelopoiesis, expression of the retinoid receptor genes (retinoic acid receptors [RARs] and retinoid X receptors [RXRs]) were examined during differentiation of factor-dependent cell-Paterson (FDCP)–mixA4 murine progenitor cells. The major receptor expressed in undifferentiated A4 cells was RARα (primarily the RARα1 isoform). Following induction of myelomonocytic differentiation with granulocyte and granulocyte-macrophage colony-stimulating factors, a dramatic increase in RARα expression (particularly the RARα2 isoform) was seen. In contrast, expression of both RARα isoforms was rapidly extinguished upon induction of erythroid differentiation with erythropoeitin (EPO). A modest induction of RXRα expression was seen, particularly during differentiation in the myelomonocytic lineage. Low expression levels of RARγ2 and RXRβ remained unchanged, irrespective of differentiation pathway. Consistent with the gene expression patterns, RARα agonists and antagonists stimulated myelomonocytic and erythroid differentiation of FDCP-mixA4 cells, respectively. Taken together, these results suggest that erythropoiesis and granulopoiesis require diminished and enhanced RARα activities, respectively, which at physiological all- trans -retinoic acid (RA) concentrations may be accomplished by reciprocal effects of EPO and myelomonocytic growth factors on its expression. This hypothesis is corroborated by data showing that RA, which positively regulates RARα2 expression, can exert inhibitory effects on erythroid differentiation.