MiR-125a Is a critical modulator for neutrophil development.
MiR-125a Is a critical modulator for neutrophil development.
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MiR-125a 是中性粒细胞发育的关键调节剂
DOI：
10.1371/journal.pgen.1007027
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发表时间：
2017-10
期刊：
影响因子：
4.5
通讯作者：
Shen N
中科院分区：
文献类型：
--
作者：
Qin Y;Wu L;Ouyang Y;Zhou P;Zhou H;Wang Y;Ma J;Zhang J;Chen Y;Qian J;Tang Y;Shen N
MicroRNA是基因组中普遍存在的转录后调节因子。它们具有缓冲基因表达程序的能力，有助于生物系统的稳健性，并在发育、生理和疾病中发挥重要作用。在这里，我们确定了一种microRNA，miR-125 a，作为粒细胞生成的正调节因子。MiR 125 a敲除小鼠显示肺中嗜中性粒细胞浸润减少，并且由于嗜中性粒细胞数量减少，内毒素攻击后组织破坏减轻。此外，我们证明，这种显着减少的中性粒细胞是由于受损的发展，粒细胞前体成熟的中性粒细胞在一个内在的方式。我们发现，Socs 3，一个关键的抑制粒细胞生成，是miR-125 a的目标。总的来说，我们的研究揭示了一种新的microRNA调节粒细胞发育，并支持miR-125 a作为粒细胞生成微调器的模型。microRNA是发育、生理和疾病过程中的关键表观遗传调节因子。许多miRNA参与免疫细胞的发育和功能，如用于B细胞的miR-150，用于T细胞的miR-181 a。然而，miRNAs参与粒细胞发育和功能以及相关疾病的研究仍然有限。在本研究中，我们开发了MiR 125 a基因敲除小鼠，以研究miR-125 a在体内的功能。我们鉴定了MiR 125 a敲除小鼠在LPS休克模型中具有减少的中性粒细胞数目和减少的中性粒细胞浸润。我们推断，这种显着减少的中性粒细胞是由于受损的发展，粒细胞前体成熟的中性粒细胞在一个内在的方式。此外，我们证明了Socs 3，一个负调节粒细胞发育的主要阻遏物，是miR-125 a的靶点。这一发现不仅揭示了一种涉及粒细胞发育的新microRNA，还为miR-125 a在内毒素血症中作用的新机制提供了见解。
MicroRNAs are universal post-transcriptional regulators in genomes. They have the ability of buffering gene expressional programs, contributing to robustness of biological systems and playing important roles in development, physiology and diseases. Here, we identified a microRNA, miR-125a, as a positive regulator of granulopoiesis. MiR125a knockout mice show reduced infiltration of neutrophils in the lung and alleviated tissue destruction after endotoxin challenge as a consequence of decreased neutrophil numbers. Furthermore, we demonstrated that this significant reduction of neutrophils was due to impaired development of granulocyte precursors to mature neutrophils in an intrinsic manner. We showed that Socs3, a critical repressor for granulopoiesis, was a target of miR-125a. Overall, our study revealed a new microRNA regulating granulocyte development and supported a model in which miR-125a acted as a fine-tuner of granulopoiesis. MicroRNAs are critical epigenetic modulators in development, physiology and disease processes. Many miRNAs are involved in immune cell development and function, like miR-150 for B cells, miR-181a for T cells. However, studies of miRNAs involvement in granulocyte development and function and related diseases are still limited. In this study, we developed engineering MiR125a knockout mice to study the function of miR-125a in vivo. We identified MiR125a knockout mice had decreased neutrophil numbers and reduced infiltration of neutrophils in the lung in LPS shock model. We deduced that this significant reduction of neutrophils was due to impaired development of granulocyte precursors to mature neutrophils in an intrinsic manner. Furthermore, we demonstrated that Socs3, a major repressor that negatively regulates granulocyte development, was a target of miR-125a. This finding not only reveals a new microRNA involving granulocyte development, but also provides insights into the new mechanism of miR-125a during action in endotoxemia.
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