生长激素通过 STAT5B 参与人类红细胞白血病和单核细胞系中 GATA1 基因的表达。

IF 2.1 4区 医学 Q3 HEMATOLOGY Blood Cells Molecules and Diseases Pub Date : 2024-09-18 DOI:10.1016/j.bcmd.2024.102894
Mana Mitsutani , Mei Yokoyama , Hiromi Hano , Aoi Morita , Midori Matsushita , Tetsuya Tagami , Kenji Moriyama
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引用次数: 0

摘要

GATA 是一个转录因子家族,由六个成员组成。据报道,GATA1 和 GATA2 尤其能促进红细胞、巨核细胞、嗜酸性粒细胞和肥大细胞的发育。然而,有关促进 GATA1 表达的细胞外配体的信息却很少。我们评估了生长激素(GH)是否是参与 GATA 信号转导的细胞外刺激物,重点研究了造血细胞系中 GATA1 的表达。我们使用了报告基因检测法、RT-PCR、实时定量 PCR 和 Western 印迹法来评估 GH 诱导的 GATA1 和 GATA2 在人红细胞白血病细胞系 K562 和非红细胞白血病细胞系 U937 中的表达。在 GH 存在的情况下,这些造血细胞系中 GATA1 的表达在转录和蛋白水平上都有所增加,并受到 STAT5 特异性抑制剂的抑制。转染了活化的 STAT5B 的细胞显示 GATA1 的表达增加。我们确定了功能性 STAT5B 共识序列,即 GATA1 启动子区域中距转录起始位点 158 bp 的结合位点。这些结果表明,GH 通过 GHR/JAK/STAT5 直接诱导 GATA1 的表达,并与造血细胞增殖有关。
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Growth hormone is involved in GATA1 gene expression via STAT5B in human erythroleukemia and monocytic cell lines
GATAs are a family of transcription factors consisting of six members. Particularly, GATA1 and GATA2 have been reported to promote the development of erythrocytes, megakaryocytes, eosinophils, and mast cells. However, little information is available on the extracellular ligands that promote GATA1 expression. We evaluated whether growth hormone (GH) is an extracellular stimulator that participates in the signal transduction of GATAs, focusing on GATA1 expression in hematopoietic cell lineages. We used a reporter assay, RT-PCR, real-time quantitative PCR, and western blotting to evaluate GH-induced expression of GATA1 and GATA2 in the human erythroleukemic cell line K562 and the non-erythroid cell line U937. GATA1 expression in these hematopoietic cell lines increased at the transcriptional and protein levels in the presence of GH, and was inhibited by a STAT5 specific inhibitor. Cells transfected with activated STAT5B showed increased expression of GATA1. We identified functional STAT5B consensus sequences as binding site-158 bp from the transcription starting site in the GATA1 promoter region. These results suggest that GH directly induces GATA1 expression via GHR/JAK/STAT5 and is related to hematopoietic cell proliferation.
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来源期刊
CiteScore
4.90
自引率
0.00%
发文量
42
审稿时长
14 days
期刊介绍: Blood Cells, Molecules & Diseases emphasizes not only blood cells, but also covers the molecular basis of hematologic disease and studies of the diseases themselves. This is an invaluable resource to all those interested in the study of hematology, cell biology, immunology, and human genetics.
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