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MiR-125a Is a critical modulator for neutrophil development
- Source :
- PLoS Genetics, Vol 13, Iss 10, p e1007027 (2017), PLoS Genetics
- Publication Year :
- 2017
- Publisher :
- Public Library of Science (PLoS), 2017.
-
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.<br />Author summary 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.
- Subjects :
- 0301 basic medicine
Cell signaling
Cancer Research
Neutrophils
Cellular differentiation
Regulator
Signal transduction
Biochemistry
White Blood Cells
Mice
Spectrum Analysis Techniques
0302 clinical medicine
Animal Cells
Granulocyte Colony-Stimulating Factor
Medicine and Health Sciences
SOCS3
3' Untranslated Regions
Genetics (clinical)
Mice, Knockout
Cell Death
Cell Differentiation
Animal Models
Flow Cytometry
Shock, Septic
Cell biology
Nucleic acids
STAT signaling
medicine.anatomical_structure
Experimental Organism Systems
Spectrophotometry
030220 oncology & carcinogenesis
Knockout mouse
Cytophotometry
Cellular Types
Research Article
lcsh:QH426-470
Immune Cells
Immunology
Bone Marrow Cells
Mouse Models
Biology
Granulocyte
Research and Analysis Methods
Models, Biological
Granulopoiesis
03 medical and health sciences
Model Organisms
microRNA
Genetics
medicine
Animals
Non-coding RNA
Molecular Biology
Myeloid Progenitor Cells
Ecology, Evolution, Behavior and Systematics
Cell Proliferation
Blood Cells
Binding Sites
Macrophages
Biology and Life Sciences
Cell Biology
Gene regulation
MicroRNAs
lcsh:Genetics
030104 developmental biology
Suppressor of Cytokine Signaling 3 Protein
RNA
Leukopoiesis
Gene expression
Granulocytes
Subjects
Details
- ISSN :
- 15537404
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- PLOS Genetics
- Accession number :
- edsair.doi.dedup.....7eda5eaa4c1d7ad8bdbdce372742dd9b