Expression profiles of long non-coding RNAs during fetal lung development.

With advances in neonatology, a greater percentage of premature infants now survive and consequently, diseases of lung development, including bronchopulmonary dysplasia and neonatal respiratory distress syndrome, have become more common. However, few studies have addressed the association between fetal lung development and long non-coding RNA (lncRNA). In the present study, right lung tissue samples of fetuses at different gestational ages were collected within 2 h of the induction of labor in order to observe morphological discrepancies. An Affymetrix Human GeneChip was used to identify differentially expressed lncRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. A total of 687 lncRNAs were identified to be differentially expressed among three groups of fetal lung tissue samples corresponding to the three embryonic periods. A total of 34 significantly upregulated and 12 significantly downregulated lncRNAs (fold-change, ≥1.5; P<0.05) were detected at different time points (embryonic weeks 7-16, 16-25 and 25-28) of fetal lung development and compared with healthy tissues Expression changes in lncRNAs n340848, n387037, n336823 and ENST00000445168 were validated by reverse transcription-quantitative PCR and the results were consistent with the GeneChip results. These novel identified lncRNAs may have roles in fetal lung development and the results of the present study may lay the foundation for subsequent in-depth studies into lncRNAs in fetal lung development and subsequent clarification of the pathogenesis of neonatal pulmonary diseases.

[Continuous expression of miR-431 during lung development in Sprague-Dawley rats].

OBJECTIVE: To study the role of miR-431 in lung development and morphology. METHODS: According to the stage of lung development in rats, Sprague-Dawley rats at embryonic day 16 (E16), embryonic day (E19), embryonic day (E21), postnatal day 1 (P1), postnatal day 3 (P3), postnatal day 7 (P7), postnatal day 14 (P14) and 10 weeks after birth (P10 weeks) were selected, and lung tissue samples were collected for observation. Hematoxylin-eosin staining and transmission electron microscopy were performed to observe the morphology of lung tissue. Fluorescence in situ hybridization and real-time PCR were used to measure the expression of miR-431 during the critical stages of lung development (E19, E21 and P3). RESULTS: The E19 group had the formation of the lamellar body and type II alveolar epithelial cells in the fetal lung tissue. The number of lamellar bodies increased with the increasing gestational age, with aggregation and excretion. Pulmonary alveoli formed rapidly, the lung interstitium became thinner, and the microvascular system became mature after birth. Fluorescence in situ hybridization and real-time PCR showed that the expression of miR-431 gradually decreased with the increasing gestational age (P<0.05). CONCLUSIONS: The systematic and continuous morphological data of lung development is obtained in this experiment. In addition, miR-431 may play an important role in the negative regulation of lung development, which provides basis and direction for further research on the mechanism of lung development and related diseases.

Knockout of microRNA­26a promotes lung development and pulmonary surfactant synthesis.

Normal formation and function of the lungs are essential for the transition of the fetus to an air­breathing environment at birth. The synthesis of pulmonary surfactant (PS), which is produced by type II alveolar epithelial cells (AECIIs), is required for proper lung development. Previous in vitro studies have suggested that PS synthesis is regulated by microRNA (miR)­26a in fetal rat AECIIs. The present study explored the potential role of miR­26a in lung development and PS synthesis by using a miR­26a­1/miR­26a­2 double knockout mouse model. Hematoxylin and eosin staining and transmission electron microscopy were used to observe the morphology of fetal lungs. Reverse transcription­quantitative polymerase chain reaction and western blot analysis were performed to examine the mRNA and protein levels of surfactant­associated proteins. The results demonstrated that the lung formation in the knockout mice was more mature, and that there were more mature lamellar bodies inside AECIIs in miR­26a knockout mice at late stages of lung development. The findings further demonstrated that knockout of miR­26a increased surfactant­associated mRNA and protein expression levels. The results indicated that knockout of miR­26a promotes lung development and PS synthesis.