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Dynamic expression and steroid regulation of sarg, a novel gene in the perinatal lung
  1. G Belteki1,2,
  2. S Kempster2,
  3. A Forhead3,
  4. A Fowden3,
  5. D S Charnock-Jones2,
  6. G C S Smith2
  1. 1Neonatal Intensive Care Unit, The Rosie Hospital, Cambridge, UK
  2. 2Departments of Obstetrics and Gynaecology, University of Cambridge, Cambridge, UK
  3. 3Departments of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK

Abstract

Background The fetal lung's preparation for birth consists of structural and physiologic maturation processes associated with underlying changes in gene expression. Understanding this gene expression program may help to develop novel therapies. Our aim was to identify novel genes up-regulated in the perinatal lung.

Methods We used the Rae230.2 oligonucleotide array to compare gene expression in embryonic day 16 and 20 rat lungs (n=10, each group). Microarray data were verified by quantitative reverse transcription PCR (qRT-PCR) in the siblings of the animals used for microarray analysis (n=10). The sheep SARG coding sequence was cloned by degenerate oligonucleotide PCR. Gene expression in sheep lungs was analysed by qRT-PCR at 100, 115, 130 and 145 days of gestation (n=5 each). The in vitro steroid induction experiments were performed in the A549 lung epithelial cell line.

Results Gene expression analysis demonstrated dramatic up-regulation of the gene SARG (‘specifically androgen responsive gene’), a gene of unknown function, in the rat lung during late gestation. Microarray and qRT-PCR analysis showed 32-fold and 42-fold up-regulation, respectively (p<0.0001 for both). The gene was also significantly up-regulated in sheep lungs during late gestation (p<0.01). Maternal dexamethasone treatment increased SARG expression 1.8-fold (p<0.01), fetal adrenalectomy reduced it 1.9-fold (p<0.01). Dexamethasone and dihydro-testosterone both significantly up-regulated SARG in A549 cells in vitro.

Conclusions SARG is an uncharacterized gene up-regulated in the perinatal lung. SARG expression is increase by both glucocorticoids and androgens. SARG may play a role in physiologic and steroid-mediated lung maturation.

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