Qin Yuting, Wu Lingling, Ouyang Ye, Zhou Ping, Zhou Haibo, Wang Yan, Ma Jianyang, Zhang Jinsong, Chen Yanan, Qian Jie, Tang Yuanjia, Shen Nan
Department of Rheumatology and Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PLoS Genet. 2017 Oct 4;13(10):e1007027. doi: 10.1371/journal.pgen.1007027. eCollection 2017 Oct.
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.
微小RNA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。在此，我们鉴定出一种微小RNA，即miR-125a，它是粒细胞生成的正向调节因子。MiR125a基因敲除小鼠肺中嗜中性粒细胞浸润减少，内毒素攻击后组织破坏减轻，这是嗜中性粒细胞数量减少的结果。此外，我们证明嗜中性粒细胞的显著减少是由于粒细胞前体向成熟嗜中性粒细胞的内在发育受损所致。我们发现，Socs3是粒细胞生成的关键抑制因子，是miR-125a的一个靶标。总体而言，我们的研究揭示了一种调节粒细胞发育的新微小RNA，并支持了一个模型，即miR-125a作为粒细胞生成的微调因子发挥作用。
