Poster Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Endogenous and Synthetic Glucocorticoid Steroids activate different but overlapping sets of target genes during mammalian lung development (#225)

Bennet Seow 1 , Annie McDougall 2 , Megan Wallace 2 , Timothy Cole 3
  1. Monash University Biochem, Clayton, VIC, Australia
  2. The Ritchie Center, MIMR-PHI Institute of Medical Research, Melbourne, VIC, Australia
  3. Biochemistry and Molecular Biology, Monash University , Melbourne, VIC, Australia

Lung immaturity is a common feature in preterm babies, which can lead to a serious condition known as respiratory distress syndrome (RDS), where the lungs of preterm infants are too immature to respire without the assistance of a mechanical ventilator. Current treatment includes antenatal injections of synthetic glucocorticoids to mothers at risk of preterm birth in an attempt to rapidly mature the fetal lung and reduce the risk of RDS. However there are some adverse side effects associated with glucocorticoid use, such as a decrease in overall fetal and brain growth and altered alveoli development. We propose that synthetic and endogenous glucocorticoids differentially regulate a specific, but different, subsets of genes in the lung which contributes to lung maturation and other adverse side effects. RNA was isolated from primary fetal rat lung fibroblast cells (at E20, term ~E22) treated for 6h with synthetic (betamethasone 10-6M) or endogenous (corticosterone 10-6M) glucocorticoids or vehicle control. Using Next Generation Sequencing (RNA-seq) we have shown that the gene expression profile is distinct for both endogenous and synthetic glucocorticoids. Synthetic glucocorticoids modulated particular genes to a higher degree compared to endogenous glucocorticoids. RNA-seq results were confirmed using qPCR;  gene targets such as Cysteine-rich secretory protein LCCL domain containing 2 (Crispld2) and SLIT-ROBO Rho GTPase activating protein 3 (Srgap3) showed a significant increase (p<0.05) in mRNA levels between control fibroblast cells and fibroblast cells treated with the corticosterone and the betamethasone These genes, respectively, play a role in alveolarization and extracellular matrix remodeling, which are important events during lung development. By gaining a better understanding of the mechanisms driving glucocorticoid mediated lung development it may be possible to development better lung-specific treatments for preterm babies that result in reducing adverse side effects, but retaining its effectiveness in inducing rapid lung maturation.