Abstract
Intrauterine growth restriction (IUGR) was recently described as an independent risk factor of bronchopulmonary dysplasia, the main respiratory sequelae of preterm birth. We previously showed impaired alveolarization in rat pups born with IUGR induced by a low-protein diet (LPD) during gestation. We conducted a genome-wide analysis of gene expression and found the involvement of several pathways such as cell adhesion. Here, we describe our unbiased microRNA (miRNA) profiling by microarray assay and validation by qPCR at postnatal days 10 and 21 (P10 and P21) in lungs of rat pups with LPD-induced lung-alveolarization disorder after IUGR. We identified 13 miRNAs with more than two-fold differential expression between control lungs and LPD-induced IUGR lungs. Validated and predicted target genes of these miRNAs were related to “tissue repair” at P10 and “cellular communication regulation” at P21. We predicted the deregulation of several genes associated with these pathways. Especially, E2F3, a transcription factor involved in cell cycle control, was expressed in developing alveoli, and its mRNA and protein levels were significantly increased at P21 after IUGR. Hence, IUGR affects the expression of selected miRNAs during lung alveolarization. These results provide a basis for deciphering the mechanistic contributions of IUGR to impaired alveolarization.
Highlights
Bronchopulmonary dysplasia (BPD) is the main respiratory sequelae of preterm birth [1]
Total RNA was obtained from five animals per group at postnatal day 10 (P10) or P21 after low-protein diet (LPD)-induced Intrauterine growth restriction (IUGR) or control diet during gestation
Analysis at P21 revealed 74 mature miRNAs with differential expression between LPD-induced IUGR rat lungs and control lungs (Fig 1): 10 showed more than twofold differential expression: miR-184, miR127-3p, miR-378a-5p and miR541-5p were downregulated, and miR-30e-5p, miR-23b-5p, miR-451-5p, miR-1839-5p, miR-449a-5p, and miR-19b-3p were upregulated in LPD-induced IUGR versus control lungs
Summary
Bronchopulmonary dysplasia (BPD) is the main respiratory sequelae of preterm birth [1].
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