Abstract
Purpose of Study: Preterm babies treated with ventilator support and supplemental oxygen frequently develop chronic lung disease (CLD) that has significant mortality and morbidity. Oxygen toxicity plays an important role in CLD etiology. Several lines of evidence have suggested that impairment of pulmonary angiogenesis is implicated in alveolization and the development of CLD. Epidermal growth factor-like domain 7 (EGFL-7) is a recently identified protein secreted from vascular endothelial cells and it regulates vascular tubulogenesis (Nature 2004;428:754). Aim of this study was to measure EGFL-7 expression in the neonatal lung during normoxia and hyperoxia.
Methods: Rat pups at 4 days of age were randomly assigned to normoxic and hyperoxic groups. The rats in the normoxic and hyperoxic groups were treated with room air and 95% O2 for 3, 6, and 10 days, respectively. The lung tissues were collected for total RNA isolation. EGFL-7 mRNA expression was measured by quantitative real-time reverse-transcription polymerase chain reaction (Q-RT-PCR). Separately, human umbilical vein endothelial cells (HUVEC) were cultured in 37°C, 5% CO2 incubator, and were exposed to normoxia (room air) or hyperoxia (95% O2).
Results EGFL-7 mRNA in normoxic neonatal rat lung was consistently expressed from 7 days to 2 months of age (n = 3) at each time. EGFL-7 mRNA expression in the hyperoxic group was significantly decreased after oxygen exposure for 3, 6 and 10 days; it decreased 2.1 fold at day 3 (n = 3); 4.1 fold at day 6 (n = 3); and 3.1 fold at day 10 (n = 3) compared to time-matched normoxic group results, respectively. EGFL-7 mRNA expression in the hyperoxic group returned to nearly normal levels 2 weeks (n = 3) after discontinuing oxygen exposure, and it remained at normal levels during the 2 month recovery period (n = 2–3). In cultured HUVEC, EGFL-7 mRNA expression also decreased 2.6 fold after 95% O2 exposure for 48 hours.
Conclusions: Oxygen exposure is associated with the decrease of EGFL-7 mRNA expression in the neonatal rat lung and the expression level returns to normal after oxygen treatment. These findings imply that reduced levels of EGFL-7 at a critical lung development stage may be a contributing factor in the impairment of pulmonary angiogenesis and alveolization after hyperoxic lung injury.
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Xu, D., Rezaiekhaligh, M., Mabry, S. et al. Expression of Epidermal Growth Factor-Like Domain 7 in Neonatal Rat Lungs During Normoxia and Hyperoxia.. Pediatr Res 56, 667 (2004). https://doi.org/10.1203/00006450-200410000-00028
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DOI: https://doi.org/10.1203/00006450-200410000-00028