title: Targeted ablation of miR-21 decreases murine eosinophil progenitor cell growth.
abstract: 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.
authors.affiliation: 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.
authors.forename: Thomas X
authors.initials: TX
authors.lastname: Lu
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Lim
authors.forename: Svetlana
authors.initials: S
authors.lastname: Itskovich
authors.forename: John A
authors.initials: JA
authors.lastname: Besse
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Plassard
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Mingler
authors.forename: Joelle A
authors.initials: JA
authors.lastname: Rothenberg
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Fulkerson
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Aronow
authors.forename: Marc E
authors.initials: ME
authors.lastname: Rothenberg
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004804:Eosinophils / Q000166:cytology*; D004941:Esophagitis / Q000235:genetics; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs