Abstract
REDD1 (Regulated in Development and DNA Damage-1) is a stress-response gene that represses mammalian target of rapamycin (mTOR) thus decreasing protein synthesis. In contrast to studies using cell lines and adult alveolar type II (ATII) cells, we find that REDD1 mRNA levels did not increase in rat fetal distal lung epithelia (FDLE) or fetal lung fibroblasts grown in primary cultures and then exposed to 3% O2. REDD1 mRNA expression was repressed by dexamethasone (DEX) in FDLE and ATII, but induced by DEX in fibroblasts. Lung epithelial cell lines, A549 and MLE-15, showed increases in REDD1 mRNA in response to hypoxia and DEX. The effect of DEX on REDD1 mRNA and protein in FDLE and fibroblasts was dose- and time-dependent. Inhibitor studies support repression of REDD1 mRNA by DEX in FDLE was mediated via glucocorticoid receptor and not by nongenomic effects of glucocorticoids via MAPK pathways. The half-life of REDD1 mRNA was shorter in DEX-exposed FDLE compared with hormone-free media suggesting that DEX reduced REDD1 mRNA stability in FDLE. These studies indicate that REDD1 expression in response to hypoxia and DEX is cell-type specific and that physiologically appropriate levels of PO2 should be used when investigating fetal lung development.
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Abbreviations
- ATII:
-
adult type II alveolar epithelial cells
- DEX:
-
dexamethasone
- FDLE:
-
fetal distal lung epithelium
- GC:
-
glucocorticoid
- GR:
-
glucocorticoid receptor
- HIF-1:
-
hypoxia inducible factor-1
- mTOR:
-
mammalian target of rapamycin
- REDD1:
-
regulated in development and DNA damage-1
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Supported by Grant MGP-25046 from the Canadian Institutes of Health Research Operating and from a Group Grant in Lung Development.
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Otulakowski, G., Duan, W., Sarangapani, A. et al. Glucocorticoid-Mediated Repression of REDD1 mRNA Expression in Rat Fetal Distal Lung Epithelial Cells. Pediatr Res 65, 514–519 (2009). https://doi.org/10.1203/PDR.0b013e3181998db6
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DOI: https://doi.org/10.1203/PDR.0b013e3181998db6
