The alveolar epithelium is composed of two morphologically distinct differentiated epithelial cells, type I and type II cells, both of which are felt to be critical for normal lung function. Type I cells are very large squamous cells which cover more than 90 percent of the alveolar surface. They are morphologically characterized by long thin cytoplasmic extensions. They provide both the tight barrier and thin diffusion pathway between the air and blood compartments that is essential for efficient gas exchange. Type II cells are small cuboidal cells which cover approximately 5 percent of the alveolar surface. They are morphologically characterized by lamellar bodies containing surfactant components, which are responsible for lowering surface tension at the alveolar air-liquid interface, preventing alveolar collapse. Type II cells also produce immune effector molecules, transport ions, and act as stem cells in alveolar epithelium is essential for life, factors controlling the expression of cellular phenotype are poorly understood. Lack of suitable cell culture models or unique cell- specific biochemical markers has made the topic difficult to approach experimentally. In recent years, considerable progress has been made in both of these areas. This project concerns the effects of mechanical forces on the regulation of phenotypic expression of the alveolar epithelium, focus on a unique rat type I cell-specific marker we have discovered and comparing the regulation of its expression to that of marker molecules for the type II cell phenotype. Intriguing recent observations, shown in the preliminary data, strongly suggest that mechanical factors play an important role in regulating phenotypic expression within the lung. The broad objectives of this proposal are two-fold: 1) to determine the effects of mechanical distention or contraction on the expression of markers for the type I and type II cell phenotypes in mature rat type II cells and in fetal rat lung explant; and 2) to define the mechanisms by which mechanical factors modulate pulmonary alveolar epithelial cell phenotypic expression in vitro.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Scientist Development Award - Research & Training (K01)
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Special Emphasis Panel (ZHL1-CSR-C (F1))
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Gutierrez, Jorge A; Suzara, Vincent V; Dobbs, Leland G (2003) Continuous mechanical contraction modulates expression of alveolar epithelial cell phenotype. Am J Respir Cell Mol Biol 29:81-7
Yoshizawa, Jyoji; Chapin, Cheryl J; Sbragia, Lourenco et al. (2003) Tracheal occlusion stimulates cell cycle progression and type I cell differentiation in lungs of fetal rats. Am J Physiol Lung Cell Mol Physiol 285:L344-53