MiR-125a Is a critical modulator for neutrophil development

Yuting Qin; Lingling Wu; Ye Ouyang; Ping Zhou; Haibo Zhou; Yan Wang; Jianyang Ma; Jinsong Zhang; Yanan Chen; Jie Qian; Yuanjia Tang; Nan Shen

doi:10.1371/journal.pgen.1007027

MiR-125a Is a critical modulator for neutrophil development

PLoS Genet. 2017 Oct 4;13(10):e1007027. doi: 10.1371/journal.pgen.1007027. eCollection 2017 Oct.

Authors

Yuting Qin¹, Lingling Wu¹, Ye Ouyang¹, Ping Zhou¹, Haibo Zhou¹, Yan Wang², Jianyang Ma¹, Jinsong Zhang², Yanan Chen¹, Jie Qian¹, Yuanjia Tang¹, Nan Shen^{1

2

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Affiliations

¹ Department of Rheumatology and Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai, China.
⁴ Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ The Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States of America.
⁶ China-Australia Centre for Personalised Immunology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

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.

MeSH terms

3' Untranslated Regions
Animals
Binding Sites / genetics
Cell Death
Cell Differentiation
Cell Proliferation
Granulocyte Colony-Stimulating Factor / metabolism
Granulocytes / cytology
Granulocytes / metabolism
Leukopoiesis / genetics*
Leukopoiesis / physiology*
Mice
Mice, Knockout
MicroRNAs / genetics*
MicroRNAs / metabolism*
Models, Biological
Myeloid Progenitor Cells / cytology
Myeloid Progenitor Cells / metabolism
Neutrophils / cytology*
Neutrophils / metabolism*
Shock, Septic / genetics
Shock, Septic / metabolism
Shock, Septic / pathology
Signal Transduction
Suppressor of Cytokine Signaling 3 Protein / genetics
Suppressor of Cytokine Signaling 3 Protein / metabolism

Substances

3' Untranslated Regions
MicroRNAs
Mirn125 microRNA, mouse
Socs3 protein, mouse
Suppressor of Cytokine Signaling 3 Protein
Granulocyte Colony-Stimulating Factor

Grants and funding

This work is supported by grants from 973 program (2014CB541902, 2014CB541901), National Natural Science Foundation of China (81230072, 81025016, 31370880, 81601440, 31630021), the Key Research Program of the Chinese Academy of Sciences (KSZD-EW-Z-003-3), as well as Chinese Ministry of Health (201202008) and the Program of the Shanghai Commission of Science and Technology (12431900703, 12JC1406000, 12ZR1435900). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.