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生长激素通过 STAT5B 参与人红白血病和单核细胞系中的 GATA1 基因表达。

Growth hormone is involved in GATA1 gene expression via STAT5B in human erythroleukemia and monocytic cell lines.

机构信息

Medicine & Clinical Science, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo 663-8179, Japan.

Clinical Research Institute for Endocrine and Metabolic Diseases, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan.

出版信息

Blood Cells Mol Dis. 2025 Feb;110:102894. doi: 10.1016/j.bcmd.2024.102894. Epub 2024 Sep 18.

DOI:10.1016/j.bcmd.2024.102894
PMID:39303396
Abstract

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.

摘要

GATAs 是一组转录因子家族,由六个成员组成。特别是,GATA1 和 GATA2 已被报道可促进红细胞、巨核细胞、嗜酸性粒细胞和肥大细胞的发育。然而,关于促进 GATA1 表达的细胞外配体的信息很少。我们评估了生长激素 (GH) 是否是一种参与 GATAs 信号转导的细胞外刺激物,重点关注 GH 在造血细胞谱系中对 GATA1 表达的影响。我们使用报告基因检测、RT-PCR、实时定量 PCR 和 Western blot 来评估 GH 诱导的人红白血病细胞系 K562 和非红细胞系 U937 中 GATA1 和 GATA2 的表达。在 GH 存在的情况下,这些造血细胞系中的 GATA1 表达在转录和蛋白水平上增加,并被 STAT5 特异性抑制剂抑制。转染激活 STAT5B 的细胞显示 GATA1 的表达增加。我们鉴定了功能 STAT5B 共有序列作为 GATA1 启动子区域转录起始位点上游的结合位点-158bp。这些结果表明,GH 通过 GHR/JAK/STAT5 直接诱导 GATA1 表达,与造血细胞增殖有关。

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