Microarray-based gene expression profiling suggests adaptation of lung epithelial cells subjected to chronic cyclic strain.

BACKGROUND/AIMS Mechanical strain of the lung tissue is a physiological process that affects the behavior of lung cells. Since recent evidence also suggests alterations in the expression of certain genes as a consequence of mechanotransduction, our study aimed at the analysis of the gene expression profile in lung epithelial cells subjected to chronic cyclic strain. METHODS Various human lung epithelial cell lines (A549 as principal adherent cell line and four others) were subjected to cyclic strain (16 % surface distension, 12 min(-1)) in a Strain Cell Culture Device for 24 h. In comparison to static controls, expression analyses were performed by gene microarray and qPCR. RESULTS Microarray analysis revealed many differences in the gene expression but at moderate levels. Altogether 25 genes were moderately down-regulated (0.86-fold ± 0.06) and 26 genes were up-regulated (1.18-fold ± 0.10) in A549 and the others. Strain-regulated genes often code for transcription factors, such as E2F4 and SRF. qPCR analyses confirmed the up-regulation of both transcription factors and further genes, such as PLAU (urokinase-type plasminogen activator) and S100A4 (S100 protein A4). Moreover, we showed the down-regulations of AGR2 (anterior gradient 2) and LCN2 (lipocalin 2). CONCLUSIONS We identified many genes of which the expression was moderately altered in lung epithelial cells subjected to chronic cyclic strain. Although many moderate changes in the gene expression profile might affect cellular behavior, it also suggests an effective adaptation of cells to mechanical forces in long-term conditions.