Back to Search
Start Over
Regulation of progenitor cell proliferation and granulocyte function by microRNA-223
- Source :
- Nature. 451(7182)
- Publication Year :
- 2007
-
Abstract
- MicroRNAs are abundant in animal genomes and have been predicted to have important roles in a broad range of gene expression programmes1,2. Despite this prominence, there is a dearth of functional knowledge regarding individual mammalian microRNAs. Using a loss-of-function allele in mice, we report here that the myeloid-specific microRNA-223 (miR-223) negatively regulates progenitor proliferation and granulocyte differentiation and activation. miR-223 (also called Mirn223) mutant mice have an expanded granulocytic compartment resulting from a cell-autonomous increase in the number of granulocyte progenitors. We show that Mef2c, a transcription factor that promotes myeloid progenitor proliferation, is a target of miR-223, and that genetic ablation of Mef2c suppresses progenitor expansion and corrects the neutrophilic phenotype in miR-223 null mice. In addition, granulocytes lacking miR-223 are hypermature, hypersensitive to activating stimuli and display increased fungicidal activity. As a consequence of this neutrophil hyperactivity, miR-223 mutant mice spontaneously develop inflammatory lung pathology and exhibit exaggerated tissue destruction after endotoxin challenge. Our data support a model in which miR-223 acts as a fine-tuner of granulocyte production and the inflammatory response.
- Subjects :
- Myeloid
Neutrophils
Granulocyte
Biology
Mice
mir-223
medicine
Gene silencing
Animals
MEF2C
Progenitor cell
Lung
Alleles
Progenitor
Cell Proliferation
Inflammation
Mice, Knockout
Multidisciplinary
MEF2 Transcription Factors
Stem Cells
Cell Differentiation
Cell biology
MicroRNAs
medicine.anatomical_structure
Phenotype
Myogenic Regulatory Factors
Immunology
Granulocyte colony-stimulating factor receptor
Gene Deletion
Granulocytes
Subjects
Details
- ISSN :
- 14764687
- Volume :
- 451
- Issue :
- 7182
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....724f5759563c7acc687e1e825bd574df