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Open Access Research article

Decreased miR-192 expression in peripheral blood of asthmatic individuals undergoing an allergen inhalation challenge

Masatsugu Yamamoto1234, Amrit Singh125, Jian Ruan12, Gail M Gauvreau6, Paul M O'Byrne6, Christopher R Carlsten234, J Mark FitzGerald234, Louis-Philippe Boulet7 and Scott J Tebbutt1235*

Author affiliations

1 UBC James Hogg Research Centre, St. Paul’s Hospital, University of British Columbia, Room 166, Burrard Building, 1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada

2 Institute for HEART+LUNG Health, Vancouver, British Columbia, Canada

3 Department of Medicine, Division of Respiratory Medicine, UBC, Vancouver, British Columbia, Canada

4 Vancouver Coastal Health Research Institute, Vancouver General Hospital, Vancouver, British Columbia, Canada

5 NCE CECR PROOF Centre of Excellence, Vancouver, British Columbia, Canada

6 Department of Medicine, McMaster University, Hamilton, Ontario, Canada

7 Centre de Pneumologie de L’Hopital, Université Laval, Sainte-Foy, Quebec, Canada

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Citation and License

BMC Genomics 2012, 13:655  doi:10.1186/1471-2164-13-655

Published: 21 November 2012

Abstract

Background

MicroRNAs are small non-coding RNAs that regulate gene expression at the post-transcriptional level. While they have been implicated in various diseases, the profile changes in allergen inhalation challenge are not clarified in human. We aimed to evaluate changes in the microRNA profiles in the peripheral blood of asthmatic subjects undergoing allergen inhalation challenge.

Results

Seven mild asthmatic subjects participated in the allergen inhalation challenge. In addition, four healthy control subjects (HCs) were recruited. MicroRNA profiles in peripheral blood samples (pre-challenge and 2 hours post-challenge) were measured by the NanoString nCounter assay to determine changes in miRNA levels as these asthmatic subjects underwent an allergen inhalation challenge. One common miRNA, miR-192, was significantly expressed in both comparisons; HCs vs. pre-challenge and pre- vs. post-challenge, showing that miR-192 was significantly under-expressed in asthmatics compared to HCs and decreased in post-challenge at an FDR of 1%. Cell-specific statistical deconvolution attributed miR-192 expression in whole blood to PBMCs. MiR-192 was technically validated using real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) showing that the level in asthmatics (pre-challenge) was significantly lower than HCs and that post-challenge was significantly lower than pre-challenge. The normalized relative miR-192 expression quantified using RT-qPCR specific to PBMCs was also validated. Ontology enrichment and canonical pathway analyses for target genes suggested several functions and pathways involved in immune response and cell cycle.

Conclusions

The miRNA profile in peripheral blood was altered after allergen inhalation challenge. Change in miR-192 levels may be implicated in asthma mechanisms. These results suggest that allergen inhalation challenge is a suitable method to characterize peripheral miRNA profiles and potentially elucidate the mechanism of human asthma.

Keywords:
Allergen inhalation challenge; Allergy; Asthma; Blood cells; Hsa-miR-192; MicroRNAs; NanoString nCounter assay