Effects of mechanical forces on lung-specific gene expression

Abstract

Fetal breathing movements (FBM) are necessary for fetal lung growth and maturation. The authors analyzed fetal rat lungs cultured with or without lung distension and tracheal ligation, and examined the effects of mechanical stretch on a human pulmonary epithelial cell line (NCI-H441) that shows regulated expression of surfactant proteins (SP-A, SP-B). Cells were grown on silastic membranes and mounted in a Flexercell Strain Unit. Cyclic deformation simulating FBM was achieved by applying a vacuum of 22 kPa (5%-15% radial deformation) at 50 cycles per minute for 2 to 24 hours. Results indicate that static distension for as little as 4 hours decreased steady-state SP-A and SP-B mRNA levels in whole lung (n = 5-6, P < .01). In contrast, cyclic stretching of H441 cells for 24 hours increased SP-B and SP-A expression 2- to 4-fold over controls. Cyclic deformation also significantly enhanced 3H-choline incorporation into saturated phosphatidylcholine. Dynamic mechanodeformation may be a critical stimulus for fetal lung development.