Am. J. Respir. Cell Mol. Biol., Volume 21, Number 2, August, 1999 223-229

Mechanical Distention Modulates Alveolar Epithelial Cell Phenotypic Expression by Transcriptional Regulation

Jorge A. Gutierrez, Robert Ertsey, Louis M. Scavo, Erin Collins, and Leland G. Dobbs

Departments of Pediatrics and Medicine and the Cardiovascular Research Institute, University of California San Francisco, San Francisco, California

The development of a normal pulmonary alveolar epithelium, essential for gas 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 regulating differentiation of the pulmonary alveolar epithelium. To test this hypothesis directly, we have investigated the in vitro effects of mechanical distention 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 messenger 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 distention 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 undistended controls. Mechanical distention had no effect on content of mRNA for SP-A or 18S ribosomal RNA. Examined by nuclear run-on assays, mechanical distention caused changes in transcriptional rates 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 phenotype; these effects occur at least in part at the transcriptional level. These studies support the hypothesis that mechanical distention of fetal lung tissue stimulates expression of the type I cell phenotype and inhibits expression of the type II phenotype.

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