Mechanical stretch promotes alveolar epithelial type II cell differentiation

Functional maturation of pulmonary alveolar epithelial cells is crucial for extrauterine survival. Mechanical distension and mesenchymal-epithelial in teractions play important roles in this process. We hypothesized that mecha nical stretch simulating fetal breathing movements is an important regulato r of pulmonary epithelial cell differentiation. Using a Flexercell Strain U nit, we analyzed effects of stretch on primary cultures of type II cells an d cocultures of epithelial and mesenchymal cells isolated from fetal rat lu ngs during late development. Cyclic stretch of isolated type II cells incre ased surfactant protein (SP) C mRNA expression by 150 +/- 30% over controls (P < 0.02) on gestational day 18 and by 130 +/- 30% on day 19 (P < 0.03). Stretch of cocultures with fibroblasts increased SP-C expression on days 18 and 19 by 170 +/- 40 and 270 +/- 40%, respectively, compared with unstretc hed cocultures. On day 19, stretch of isolated type II cells increased SP-B mRNA expression by 50% (P < 0.003). Unlike SP-C, addition of fibroblasts d id not produce significant additional effects on SP-B mRNA levels. Under th ese conditions, we observed only modest increases in cellular immunoreactiv e SP-B, but secreted saturated phosphatidylcholine rose by 40% (P < 0.002). These results indicate that cyclic stretch promotes developmentally timed differentiation of fetal type II cells, as a direct effect on epithelial ce ll function and via mesenchymal-epithelial interactions. Expression of the SP-C gene appears to be highly responsive to mechanical stimulation.