Of mice and men: correlations between microRNA-17∼92 cluster expression and promoter methylation in severe bronchopulmonary dysplasia
| Autor: | Clay B. Marsh, Mary E. Robbins, Duaa Dakhlallah, Trent E. Tipple, Lynette K. Rogers |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Pulmonary and Respiratory Medicine Physiology Hyperoxia Biology DNA methyltransferase Pathogenesis Andrology Mice 03 medical and health sciences 0302 clinical medicine Physiology (medical) mental disorders microRNA medicine Animals Humans DNA (Cytosine-5-)-Methyltransferases Promoter Regions Genetic Lung Bronchopulmonary Dysplasia Inflammation Regulation of gene expression Rapid Report Infant Newborn Cell Biology Methylation DNA Methylation medicine.disease Disease Models Animal MicroRNAs 030104 developmental biology Gene Expression Regulation 030228 respiratory system Bronchopulmonary dysplasia DNA methylation Immunology Female RNA Long Noncoding medicine.symptom |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 311:L981-L984 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.00390.2016 |
| Popis: | We previously demonstrated that decreased miR-17∼92 cluster expression was 1) present in lungs from human infants who died with bronchopulmonary dysplasia (BPD); 2) inversely correlated with DNA methyltransferase (DNMT) expression and promoter methylation; and 3) correlated with a subsequent diagnosis of BPD at 36 wk gestational age. We tested the hypothesis that plasma miR-17 levels would be lowest in infants who ultimately develop severe BPD. Secondly, we utilized our well-characterized murine model of severe BPD that combines perinatal inflammation with postnatal hyperoxia to test the hypothesis that alterations in lung miR-17∼92, DNMT, and promoter methylation in our model would mirror our findings in tissues from premature human infants. Plasma was obtained during the first 5 days of life from premature infants born ≤32 wk gestation. Lung tissues were harvested from mice exposed to maternal inflammation and neonatal hyperoxia for 14 days after birth. miR-17∼92 cluster expression and DNA methyltransferase expression were measured by qRT-PCR, and promoter methylation was assessed by Methyl-Profiler assay. Plasma miR-17 levels are significantly lower in the first week of life in human infants who develop severe BPD compared with mild or moderate BPD. Data from our severe BPD murine model reveal that lung miR-17∼92 cluster expression is significantly attenuated, and levels inversely correlated with DNMT expression and miR-17∼92 cluster promoter methylation. Collectively, our data support a plausible role for epigenetically altered miR-17∼92 cluster in the pathogenesis of severe BPD. |
| Databáze: | OpenAIRE |
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