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Continuous Mechanical Contraction Modulates Expression of Alveolar Epithelial Cell Phenotype

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

Address correspondence to: Jorge A. Gutierrez, Department of Pediatrics, University of California, San Francisco, 3333 California St., Suite 150, San Francisco, CA 94118. E-mail: jgut{at}itsa.ucsf.edu

We have previously reported that mechanical distention of alveolar epithelial type II cells in culture favored the expression of the type I cell phenotype and inhibited the expression of the type II cell phenotype. The objective of the present study was to investigate the effects of continuous mechanical contraction on the expression of specific markers for the type I and type II cell phenotypes in cultured alveolar type II cells. Type II cells were mechanically contracted in culture at varying amplitudes and times. Cells were analyzed for mRNA and protein content of markers of the type I (RTI40) and type II (surfactant proteins [SPs] A, B, and C) phenotypes. Continuous contraction of culture membrane surface area by 25% for a duration of 4 h resulted in an 83% increase in SP-A, a 42% increase in SP-B, and a 230% increase in SP-C, in comparison with controls. After 12 h of contraction, RTI40 mRNA content decreased to 59% of control levels. A minimal contraction of 20% of culture membrane surface area was required to modulate expression of the type II cell markers. In summary, mechanical contraction favors expression of the type II cell phenotype and inhibits expression of the type I cell phenotype in a time- and amplitude-dependent manner.

Abbreviations: phosphate-buffered saline, PBS • surfactant protein, SP • tris-buffered saline containing 0.05% Tween, TBS-T

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