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Open Access Research article

Micro-RNAs in regenerating lungs: an integrative systems biology analysis of murine influenza pneumonia

Kai Sen Tan12, Hyungwon Choi3, Xiaoou Jiang1, Lu Yin2, Ju Ee Seet4, Volker Patzel15, Bevin P Engelward26 and Vincent T Chow12*

Author Affiliations

1 Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 5 Science Drive 2, Kent Ridge 117545, Singapore

2 Infectious Diseases Interdisciplinary Research Group, Singapore-Massachusetts Institute of Technology Alliance in Research and Technology, Kent Ridge 138602, Singapore

3 Saw Swee Hock School of Public Health, National University of Singapore, Kent Ridge 117597, Singapore

4 Department of Pathology, National University Hospital, Kent Ridge 119074, Singapore

5 Department of Medicine, University of Cambridge, Cambridge CB2 0SP, UK

6 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

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BMC Genomics 2014, 15:587  doi:10.1186/1471-2164-15-587

Published: 11 July 2014

Abstract

Background

Tissue regeneration in the lungs is gaining increasing interest as a potential influenza management strategy. In this study, we explored the role of microRNAs, short non-coding RNAs involved in post-transcriptional regulation, during pulmonary regeneration after influenza infection.

Results

We profiled miRNA and mRNA expression levels following lung injury and tissue regeneration using a murine influenza pneumonia model. BALB/c mice were infected with a sub-lethal dose of influenza A/PR/8(H1N1) virus, and their lungs were harvested at 7 and 15 days post-infection to evaluate the expression of ~300 miRNAs along with ~36,000 genes using microarrays. A global network was constructed between differentially expressed miRNAs and their potential target genes with particular focus on the pulmonary repair and regeneration processes to elucidate the regulatory role of miRNAs in the lung repair pathways. The miRNA arrays revealed a global down-regulation of miRNAs. TargetScan analyses also revealed specific miRNAs highly involved in targeting relevant gene functions in repair such as miR-290 and miR-505 at 7 dpi; and let-7, miR-21 and miR-30 at 15 dpi.

Conclusion

The significantly differentially regulated miRNAs are implicated in the activation or suppression of cellular proliferation and stem cell maintenance, which are required during the repair of the damaged lungs. These findings provide opportunities in the development of novel repair strategies in influenza-induced pulmonary injury.

Keywords:
Lung repair; Pulmonary regeneration; Influenza pneumonia; miRNAs; miRNome; Transcriptome