Exposure of high concentration oxygen inhibits Sox17 expression in vascular endothelial cells of neonatal mice lungs

Abstract

Objective To study the effects of high concentration oxygen exposure on the Sox17 expression of vascular endothelial cells of neonatal mice lungs, and to explore the pathogenesis of blocked lung vascular development. Methods Thirty two C57Bl/6J newborn mice within six hours after birth were randomly divided to hyperoxia group (n=16) and room air group (n=16). Mice of hyperoxia group were exposed to 85% oxygen. Eight mice of either group were sacrificed at 7 and 14 days after birth respectively to observe the lung morphology and calculate radial alveolar counts (RAC), which is the number of alveoli on the straight line from the center of respiratory bronchioles to the nearest fibrous septa or the pleura. Sox17 expression in the pulmonary vessels was detected by immunohistochemical staining. Sox17 mRNA was measured by reverse transcription polymerase chain reaction. Sox17 protein level was measured by Western blot. Two independent samples t-test was used for statistical analysis. Results Compared with day 7, the lung structures matured with more uniformed alveoli and the septas became thinner on day 14 in room air group. However, the lungs developed slowly with simplified and non-uniformed alveoli on day 14 in hyperoxia group. The Sox17 protein was positive on endothelial cells of pulmonary arteries, veins and alveolar capillarys, as well as the alveolar epithelial cells.The RAC on day 7 and day 14 in hyperoxia group were both lower than that in room air group (3.7±0.7 vs 5.0±0.8, 5.3±0.6 vs 8.3±0.9, respectively, t=3.057 and 8.148, both P<0.01 ). Sox17 mRNA on day 7 and day 14 in hyperoxia group were both lower than that in room air group (0.62±0.10 vs 0.88±0.11, 0.44±0.06 vs 0.90±0.15, t=3.607 and 6.926, both P<0.01). Sox17 protein level on day 7 and day 14 in hyperoxia group were both lowered than that in room air group (0.32±0.04 vs 0.76±0.04, 0.36±0.07 vs 0.96±0.06, t=3.102 and 8.421, both P<0.01 ). Conclusions Exposure of high concentration of oxygen may cause impairment of lung vascular development by inhibiting Sox17 expression in lungs of neonatal mice. Key words: Bronchopulmonary dysplasia; SoxF transcription factors; Endothelium, vascular; Animals, newborn; Mice