CYCLIC MECHANICAL DEFORMATION STIMULATES HUMAN LUNG FIBROBLAST PROLIFERATION AND AUTOCRINE GROWTH-FACTOR ACTIVITY

Cellular hypertrophy and hyperplasia and increased extracellular matri x deposition are features of tissue hypertrophy resulting from increas ed work load. It is known, for example, that mechanical forces play a critical role in lung development, cardiovascular remodeling following pressure overload, and skeletal muscle growth. The mechanisms involve d in these processes, however, remain unclear. Here we examined the ef fect of mechanical deformation on fibroblast function in vitro. IMR-90 human fetal lung fibroblasts grown on collagen-coated silastic membra nes were subjected to cyclical mechanical deformation (10% increase in culture surface area; 1 Hz) for up to 5 days. Cell number was increas ed by 39% after 2 days of deformation (1.43 +/- 0.01 x 10(5) cells/mem brane compared with control, 1.03 +/- 0.02 x 10(5) cells; mean +/- SEM ; P < 0.02) increasing to 163% above control by 4 days (2.16 +/- 0.16 x 10(5) cells compared with 0.82 +/- 0.03 x 10(5) cells; P < 0.001). T he medium from mechanically deformed cells was mitogenic for IMR-90 ce lls, with maximal activity in the medium from cells mechanically defor med for 2 days (stimulating cell replication by 35% compared with medi a control; P < 0.002). These data suggest that mechanical deformation stimulates human lung fibroblast replication and that this effect is m ediated by the release of autocrine growth factors.