Mechanical distention modulates alveolar epithelial cell phenotypic expression by transcriptional regulation

The development of a normal pulmonary alveolar epithelium, essential for ga s exchange, is critical for the successful adaptation to extrauterine life. From observations of natural and experimental developmental abnormalities, it has been hypothesized that mechanical factors may play a role in regula ting differentiation of the pulmonary alveolar epithelium. To test this hyp othesis directly, we have investigated the in vitro effects of mechanical d istention on the expression of specific markers for the type I and type II cell phenotypes. Fetal rat lung (18-d) explants were mechanically distended in culture for 18 h. Mechanical distention caused an increase in RTI 40 me ssenger RNA (mRNA), a marker of the type I cell phenotype, of 10.6 times (n = 3, P < 0.05) that of undistended controls. In contrast, mechanical diste ntion resulted in a decrease in mRNA content of two markers of the type II cell phenotype, surfactant protein (SP)-B and SP-C. SP-B was reduced to 10 +/- 9% (n = 3, P < 0.005) and of SP-C to 12 +/- 7% (n = 3, P < 0.0001) of u ndistended controls. Mechanical distention had no effect on content of mRNA for SP-A or 18S ribosomal RNA. Examined by nuclear run-on assays, mechanic al distention caused changes in transcriptional fates of RTI 40, SP-B, and SP-C. These data show that mechanical distention stimulates expression of a type I cell marker and inhibits expression of markers for the type II phen otype; these effects occur at least in part at the transcriptional level. T hese studies support the hypothesis that mechanical distention of fetal lun g tissue stimulates expression of the type I cell phenotype and inhibits ex pression of the type II phenotype.