MicroRNA expression profiles and target prediction in neonatal Wistar rat lungs during the development of bronchopulmonary dysplasia

摘要

In this study, we investigated the mechanisms through which microRNAs (miRNAs or miRs) regulate lung development after birth, as well as the role of miRNAs in the development of bronchopulmonary dysplasia (BPD). For this purpose, a total of 90 neonatal Wistar rats were randomly and equally assigned to either a model group or a control group. On postnatal days 3, 7 and 14, the lung tissues were collected for histological analysis to determine morphological changes. The expression levels of proliferating cell nuclear antigen (PCNA) and platelet endothelial cell adhesion molecule-1 (PECAM-1, also known as CD31) were measured by RT-qPCR and western blot analysis. A miRCURY™ LNA array was employed to screen for differentially expressed miRNAs, and the possible target genes of those miRNAs were predicted. Our results revealed that, compared with the control group, the following changes induced by hyperoxia were observed in the model group over time: a decrease in the number, but an increase in the size of the alveoli, and a decrease in the number of secondary septa formed. In the model group, from postnatal days 3–14, the mRNA and protein expression levels of PCNA and CD31 were significantly lower than those in the control group. The differentially expressed miRNAs between the 2 groups were identified on days 3, 7 and 14 after birth. Possible target genes were identified for 32 differentially expressed miRNAs. Taken together, these findings suggest that during the development of BPD, an alveolarization disorder with microvascular dysplasia co-exists with the differential expression of certain miRNAs during the different stages of alveolar development in a neonatal rat model of hyperoxia-induced BPD. This indicates that miRNAs may participate in the occurrence and development of BPD.