Targeted ablation of miR-21 decreases murine eosinophil progenitor cell growth.

Autor: Lu TX; Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America., Lim EJ, Itskovich S, Besse JA, Plassard AJ, Mingler MK, Rothenberg JA, Fulkerson PC, Aronow BJ, Rothenberg ME
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2013; Vol. 8 (3), pp. e59397. Date of Electronic Publication: 2013 Mar 22.
DOI: 10.1371/journal.pone.0059397
Abstrakt: MiR-21 is one of the most up-regulated miRNAs in multiple allergic diseases associated with eosinophilia and has been shown to positively correlate with eosinophil levels. Herein, we show that miR-21 is up-regulated during IL-5-driven eosinophil differentiation from progenitor cells in vitro. Targeted ablation of miR-21 leads to reduced eosinophil progenitor cell growth. Furthermore, miR-21(-/-) eosinophil progenitor cells have increased apoptosis as indicated by increased levels of annexin V positivity compared to miR-21(+/+) eosinophil progenitor cells. Indeed, miR-21(-/-) mice have reduced blood eosinophil levels in vivo and reduced eosinophil colony forming unit capacity in the bone marrow. Using gene expression microarray analysis, we identified dysregulation of genes involved in cell proliferation (e,g, Ms4a3, Grb7), cell cycle and immune response as the most significant pathways affected by miR-21 in eosinophil progenitors. These results demonstrate that miR-21 can regulate the development of eosinophils by influencing eosinophil progenitor cell growth. Our findings have identified one of the first miRNAs with a role in regulating eosinophil development.
Databáze: MEDLINE