Transcriptional responses of neonatal mouse lung to hyperoxia by Nrf2 status

新生小鼠肺对高氧的转录反应与 Nrf2 状态

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作者:Sharon A McGrath-Morrow, Thomas Lauer, Joseph M Collaco, Armando Lopez, Deepti Malhotra, Yuriy O Alekseyev, Enid Neptune, Robert Wise, Shyam Biswal

Conclusion

p21/p53 pathways gene expression was not attenuated by Nrf2 activation in neonatal lung. In utero SUL did not attenuate p21 expression in wildtype neonatal lung exposed to hyperoxia. These findings suggest that although Nrf2 activation induces expression of anti-oxidant genes, it does not attenuate alveolar growth arrest caused by exposure to hyperoxia.

Methods

Microarray analysis was performed in neonatal Nrf2(+/+) and Nrf2(-/-) lungs exposed to one and 3days of hyperoxia. Sulforaphane, an inducer of Nrf2 was given to timed pregnant mice to determine if in utero exposure attenuated p21 and IL-6 gene expression in wildtype neonatal mice exposed to hyperoxia.

Results

Cell cycle regulatory genes were induced in Nrf2(-/-) lung at 1day of hyperoxia. At 3days of hyperoxia, induction of cell cycle regulatory genes was similar in Nrf2(+/+) and Nrf2(-/-) lungs, despite higher inflammatory gene expression in Nrf2(-/-) lung.

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