Liver kinase B1 (LKB1) in murine erythroid progenitors modulates erythropoietin setpoint in association with maturation control

IF 2.1 4区 医学 Q3 HEMATOLOGY
Zollie White III, Kamaleldin E. Elagib, Alejandro A. Gru, Adam N. Goldfarb
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引用次数: 0

Abstract

Erythropoiesis is a tightly regulated process. It is stimulated by decreased oxygen in circulation, which leads to the secretion of the hormone erythropoietin (Epo) by the kidneys. An additional layer of control involves the coordinated sensing and use of nutrients. Much cellular machinery contributes to sensing and responding to nutrient status in cells, and one key participant is the kinase LKB1. The current study examines the role of LKB1 in erythropoiesis using a murine in vivo and ex vivo conditional knockout system. In vivo analysis showed erythroid loss of LKB1 to be associated with a robust increase in serum Epo and mild reticulocytosis. Despite these abnormalities, no evidence of anemia or hemolysis was found. Further characterization using an ex vivo progenitor culture assay demonstrated accelerated erythroid maturation in the LKB1-deficient cells. Based on pharmacologic evidence, this phenotype appeared to result from impaired AMP-activated protein kinase (AMPK) signaling downstream of LKB1. These findings reveal a role for LKB1 in fine-tuning Epo-driven erythropoiesis in association with maturational control.

小鼠红细胞祖细胞中的肝激酶B1 (LKB1)调节与成熟控制相关的促红细胞生成素设定点
红细胞生成是一个受到严格调控的过程。血液循环中的氧气减少会刺激红细胞生成,从而导致肾脏分泌促红细胞生成素(Epo)。另一层控制包括对营养物质的协调感知和使用。许多细胞机制有助于感知和响应细胞中的营养状态,其中一个关键参与者是LKB1激酶。目前的研究使用小鼠体内和体外条件敲除系统检查LKB1在红细胞生成中的作用。体内分析显示,红细胞LKB1的缺失与血清促红细胞生成素的显著增加和轻度网状红细胞缺乏症有关。尽管有这些异常,但没有发现贫血或溶血的证据。利用离体祖细胞培养实验进一步表征表明,lkb1缺陷细胞的红系成熟加速。基于药理学证据,这种表型似乎是由于LKB1下游amp活化蛋白激酶(AMPK)信号通路受损所致。这些发现揭示了LKB1在与成熟控制相关的微调epod驱动的红细胞生成中的作用。
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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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