Abstract
Background:
We currently do not know how the herbicide nitrofen induces lung hypoplasia and congenital diaphragmatic hernia in rats. Our aim was to compare the differentially expressed transcriptome of nitrofen-induced hypoplastic lungs to control lungs in embryonic day 13 rat embryos before the development of embryonic diaphragmatic defects.
Methods:
Using next-generation sequencing technology, we identified the expression profile of microRNA (miRNA) and mRNA genes. Once the dataset was validated by both RT-qPCR and digital-PCR, we conducted gene ontology, miRNA target analysis, and orthologous miRNA sequence matching for the deregulated miRNAs in silico.
Results:
Our study identified 186 known mRNA and 100 miRNAs which were differentially expressed in nitrofen-induced hypoplastic lungs. Sixty-four rat miRNAs homologous to known human miRNAs were identified. A subset of these genes may promote lung hypoplasia in rat and/or human, and we discuss their associations. Potential miRNA pathways relevant to nitrofen-induced lung hypoplasia include PI3K, TGF-β, and cell cycle kinases.
Conclusion:
Nitrofen-induced hypoplastic lungs have an abnormal transcriptome that may lead to impaired development.
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Acknowledgements
We would like to thank Dr. Deborah Tsuyuki, Manager of the Next Generation Sequencing Platform at the Children’s Hospital Research Institute of Manitoba for her technical assistance. This work was supported by a small grant from the Children’s Hospital Research Institute of Manitoba. Richard Keijzer holds a career enhancement award from the Canadian Child Health Clinician Scientist Program and a New Investigator Salary Award from the Canadian Institutes of Health Research and Manitoba Lung Association/Children’s Hospital Research Institute of Manitoba.
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Mahood, T., Johar, D., Iwasiow, B. et al. The transcriptome of nitrofen-induced pulmonary hypoplasia in the rat model of congenital diaphragmatic hernia. Pediatr Res 79, 766–775 (2016). https://doi.org/10.1038/pr.2015.277
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DOI: https://doi.org/10.1038/pr.2015.277
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