title: Dietary flaxseed modulates the miRNA profile in irradiated and non-irradiated murine lungs: a novel mechanism of tissue radioprotection by flaxseed.
abstract: BACKGROUND
  Dietary flaxseed (FS) displays antioxidant and anti-inflammatory properties in preclinical models of lung disease including radiation-induced pneumonopathy, however the mechanisms of lung radioprotection are incompletely understood. MicroRNAs (miRNAs) are short oligonucleotides that act as important posttranscriptional regulators of diverse networks including inflammatory response networks. Responses of miRNA profiles to diet and radiation exposure have been reported, but the potential contribution of miRNAs to diet-related radioprotection has never been tested.
  
  
  METHODS
  In this exploratory pilot study, mice were fed 10% FS or a 0% FS isocaloric control diet and exposed to a single-fraction 13.5 Gy thoracic X-ray radiation treatment (XRT). Lung RNA was extracted 48 h post-XRT and small RNAs profiled by OpenArray.
  
  
  RESULTS
  FS significantly modulated expression of multiple miRNAs, including 7 with P<0.001. miR-150 was downregulated approximately 2.9-fold in the FS groups and is disproportionately integrated into immune response-related networks. Although few miRNAs were significantly changed by radiation, interaction between diet and radiation was observed. For example, miR-29c was greatly downregulated in the FS/Control group (10- to 50-fold) but slightly upregulated in the FS/radiation group. Compared with FS/control, the FS/radiation group experienced a 50% decrease of the p53-responsive miR-34a, which regulates senescence- and apoptosis-related factors.
  
  
  CONCLUSIONS
  FS induced significant changes in lung miRNA profile suggesting that modulation of small RNA by dietary supplements may represent a novel strategy to prevent adverse side-effects of thoracic radiotherapy. This pilot study provides insight into a potential mechanism of flaxseed's radioprotection and provides a useful model-system to further explore and optimize such small RNA-based therapies.
authors.affiliation: Department of Medicine, Pulmonary Allergy and Critical Care Division; Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Melpo
authors.initials: M
authors.lastname: Christofidou-Solomidou
authors.affiliation: Department of Medicine, Pulmonary Allergy and Critical Care Division; Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Pietrofesa
authors.affiliation: Department of Medicine, Pulmonary Allergy and Critical Care Division; Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Evguenia
authors.initials: E
authors.lastname: Arguiri
authors.affiliation: Department of Molecular and Comparative Pathobiology; Johns Hopkins University School of Medicine; Baltimore, MD USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: McAlexander
authors.affiliation: Department of Molecular and Comparative Pathobiology; Johns Hopkins University School of Medicine; Baltimore, MD USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Witwer
mesh_terms: D000818:Animals; D004032:Diet; D019597:Flax; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008517:Phytotherapy; D010865:Pilot Projects; D012639:Seeds
chemical_list: D035683:MicroRNAs
keywords: ROS; antioxidant; flaxseed; inflammation; lung fibrosis; lung injury; miR-150; miR-29c; miR-34a; miRNA; mouse model; radiation pneumonopathy
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