Effect of Carbon Dioxide on Neonatal Mouse Lung: A Genomic Approach

Rationale: Despite the deleterious effects associated with elevated carbon dioxide (CO2), or hypercapnia, it has been hypothesized that CO2 can protect the lung from injury. However, the effects of chronic hypercapnia on the neonatal lung are unknown. Objectives: To determine whether chronic hypercapnia alters alveolar development and to identify genes that could potentially contribute to hypercapnia-mediated lung protection. Methods: Newborn mouse litters were exposed to 8% CO2, 12% CO2 or room air for 2 weeks. Lungs were excised and analyzed for morphometric alterations. Gene expression changes were assessed by microarray techniques and RT-PCR, and gene products by western blotting. Results: The alveolar walls of CO2-exposed mice appeared thinner than those of controls. In addition, genes from a variety of functional categories were differentially expressed with hypercapnia, including those involved with cell growth/maintenance, signal transduction, protein metabolism, ion transport, stress response and inflammation. In particular and of major interest, gene expression was increased for surfactant proteins (SP) A and D, epithelial Na+ channel, GATA binding protein 6 and fibroblast growth factor receptor 2. In addition, SP-A and SP-D protein expression was increased with hypercapnia. Conclusions: Our results lead us to conclude that: 1) There are potentially a number of gene families which may contribute to hypercapnia-mediated lung protection, and 2) up-regulation of SP-A and SP-D may play a role as anti-inflammatory or antioxidant agents. Based on our genomic results, the effects of CO2 depend on the level to which the lung is exposed. Keywords: stress response Total 5 arrays including 2 dye-swaps were performed for the 8% CO2 treated animals. Five individual animals were analyzed. Total 4 arrays including 2 dye-swaps were performed for the 12% CO2 treated animals. Four individual animals were analyzed.