Lung microRNA deregulation associated with impaired alveolarization in rats after intrauterine growth restriction

Pauline Dravet-Gounot1,2,3,4,5, Cécile Morin1,2,3,5, Sébastien Jacques1,2,3

  • 1Inserm, U1016, Institut Cochin, Paris, France.

Plos One
|December 30, 2017
PubMed

Insights

Intrauterine growth restriction (IUGR) impairs lung development in preterm infants. This study reveals specific microRNAs (miRNAs) are altered in IUGR, affecting lung repair and communication, offering insights into bronchopulmonary dysplasia.

Area of Science:

  • Respiratory Medicine
  • Developmental Biology
  • Molecular Biology

Background:

  • Intrauterine growth restriction (IUGR) is a risk factor for bronchopulmonary dysplasia (BPD), a major complication of preterm birth.
  • Previous studies demonstrated impaired lung alveolarization in IUGR rat models.
  • Genome-wide analysis suggested involvement of cell adhesion pathways in IUGR-induced lung changes.

Purpose of the Study:

  • To investigate microRNA (miRNA) expression profiles in the lungs of IUGR rat pups.
  • To identify specific miRNAs and their target genes involved in lung alveolarization disorders caused by IUGR.
  • To elucidate the mechanistic contribution of IUGR to impaired lung development.

Main Methods:

  • Unbiased microRNA (miRNA) profiling using microarray assays in rat pups.
  • Quantitative real-time PCR (qPCR) for miRNA validation at postnatal days 10 and 21.
  • Bioinformatic analysis to predict target genes and associated pathways.

Main Results:

  • Identified 13 differentially expressed miRNAs ( > 2-fold change) in IUGR versus control lungs.
  • miRNA targets were associated with "tissue repair" at P10 and "cellular communication regulation" at P21.
  • Found increased mRNA and protein levels of E2F3, a cell cycle regulator, in IUGR lungs at P21.

Conclusions:

  • IUGR significantly alters miRNA expression during lung alveolarization.
  • Specific miRNAs and their targets play a role in IUGR-related lung development impairment.
  • Findings provide a foundation for understanding IUGR's role in bronchopulmonary dysplasia.

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