关键词: GATA2 Growth hormone Growth hormone receptor Signal transduction Transcription factors

Mesh : Mice Animals Growth Hormone / metabolism STAT5 Transcription Factor / genetics metabolism Janus Kinases / metabolism Signal Transduction STAT Transcription Factors / metabolism Human Growth Hormone / metabolism Milk Proteins

来  源:   DOI:10.1016/j.ghir.2024.101572

Abstract:
OBJECTIVE: GATA2 is a key transcription factor involved in the differentiation and determination of thyrotrophs and gonadotrophs in pituitary and hematopoietic development. However, studies on the upstream ligands of the GATA2 signal transduction pathway have been limited. To identify upstream ligands, we examined growth hormone (GH) as a plausible stimulator.
METHODS: We evaluated GH-induced GATA2 expression in murine TtT/GF thyrotrophic pituitary tumor cells and its direct impact on the GHR/JAK/STAT5 pathway using a combination of a reporter assay, real-time quantitative polymerase chain reaction, and western blotting.
RESULTS: GATA2 expression increased with activated STAT5B in a dose-dependent manner and was inhibited by a STAT5 specific inhibitor. Moreover, we found functional STAT5B binding site consensus sequences at -359 bp in the GATA2 promoter region.
CONCLUSIONS: These findings suggest that GH directly stimulates GATA2 via the GHR/JAK/STAT pathway and participates in various developmental phenomena mediated by GATA2.
摘要:
目的:GATA2是参与促甲状腺激素和促性腺激素的分化和决定的关键转录因子。然而,对GATA2信号转导途径上游配体的研究有限。为了识别上游配体,我们检查了生长激素(GH)作为一种合理的刺激剂。
方法:我们使用报告基因分析的组合,评估了GH诱导的GATA2在鼠TtT/GF甲状腺营养性垂体瘤细胞中的表达及其对GHR/JAK/STAT5途径的直接影响,实时定量聚合酶链反应,和西方印迹。
结果:GATA2表达随STAT5B的激活而呈剂量依赖性增加,并被STAT5特异性抑制剂抑制。此外,我们在GATA2启动子区-359bp处发现功能性STAT5B结合位点共有序列.
结论:这些发现表明GH通过GHR/JAK/STAT途径直接刺激GATA2,并参与GATA2介导的各种发育现象。
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