Calcyclin gene expression is increased by mechanical strain in fibroblastsand lung

Mechanical tension extending throughout the structural elements of the lung is a potential stimulus for cell proliferation and gene expression. Pulmon ary fibroblasts located in the interstitial space of the capillary wall thr oughout the lung parenchyma and within the large vessels and airways are un iquely situated to sense changes in mechanical force. Therefore, we used th e polymerase chain reaction-based method of differential display analysis t o screen for altered gene expression in fetal human lung fibroblasts expose d to increased cyclic stretch. IMR-90 cells were seeded at 3 X 10(4) cells/ cm(2) on laminin-coated plates. Cells were subsequently exposed to mechanic al strain on a Flexercell apparatus, resulting in a maximal elongation of 2 0% at a rate of 60 cycles/min over a period of 48 h. A complementary DNA co rresponding to the cell cycle-regulated gene calcyclin was identified in me chanically strained fibroblasts, Increased calcyclin messenger RNA levels w ere confirmed by Northern blot analysis. Further, calcyclin gene expression was upregulated in isolated-perfused rat lungs exposed to increased mechan ical strain by ventilation at high states of lung inflation for 4 h. These data suggest that calcyclin gene expression plays a role in the response of pulmonary fibroblasts to increased mechanical tension and may alter the re gulation of the fibroblast cell cycle. Breen, E. C., Z. Fu, and H. Normand. 1999. Calcyclin gene expression is increased by mechanical strain in fibro blasts and lung.