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Accession IconGSE14917

C/EBPa is required for pulmonary cytoprotection from hyperoxia injury

Organism Icon Mus musculus
Sample Icon 18 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

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Description
We have previously demonstrated that deletion of the Cebpa gene in the developing fetal mouse lung caused death soon after birth from the failure of lung maturation. Many of the transcriptional pathways regulating morphogenesis of the fetal lung are induced postnatally and mediate repair of the injured lung. We hypothesized that C/EBPa plays a role in protection of the alveolar epithelium following hyperoxia injury of the mature lung. Transgenic Cebpa/ mice in which Cebpa was conditionally deleted from Clara cells (from early gestation) and type II cells (from near-term) were developed. Cebpa/ mice grow normally without any pulmonary abnormalities. Cebpa/ mice were highly susceptible to hyperoxia. Cebpa/ mice died within 4d after hyperoxia associated with severe lung inflammation and altered surfactant components at a time when all control mice survived. Microarrays were analyzed on isolated type II cells at an early stage (24h) of hyperoxia exposure to detect the primary genes influenced by deletion of Cebpa. The associated network analysis revealed the reduced expression of key genes related to surfactant lipid and protein homeostasis, such as Srebf, Scap, Lpcat1, Abca3, Sftpb, and Napsa. Genes for the cell signaling, immune response, and protective antioxidants, including GSH and Vnn-1,3, were decreased in the Cebpa/ mice lung. C/EBPa did not play a critical role in postnatal pulmonary function under normal conditions. In contrast, in the absence of C/EBPa, exposure to hyperoxia caused respiratory failure, supporting the concept that C/EBPa plays an important role in enhancing epithelial cell survival, surfactant lipid homeostasis, and maturation of SP-B from pro-SP-B.
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18
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