Identification of cellular processes that are rapidly modulated in response to tracheal occlusion within mice lungs.

Lung development progresses through a process reliant on mechanical cell stretch. However, this process is not well defined at the molecular level. Our goal was to globally analyze the transcriptome of fetal mouse lungs following short periods of tracheal occlusion (TO) to identify cellular processes that are rapidly modulated in response to intraluminal stretch increase. Serial analysis of gene expression (SAGE) was used to examine the global transcriptomic response of mouse prealveolar stage lungs to in vivo TO at 1 and 3 h. SAGE results were extended by histo- and immunochemical examination. Based on the 97 TO-modulated transcripts identified, our results further point out that continuous stretch in developing lungs leads directly to rapid and highly specific phenotypic modifications in a significant proportion of pulmonary cells. We conclude that intraluminal stretch increase during prealveolar stage of lung development induces a critical transition of pulmonary cells phenotype in which there is an increase in α-smooth muscle actin (α-SMA)–containing cells along with a relative decrease in lipid-containing cells.