Ressler B, Lee RT, Randell SH, Drazen JM, Kamm RD. 2000. Molecular responses of rat tracheal epithelial cells to transmembrane pressure. American journal of physiology. Lung cellular and molecular physiology. 278(6):L1264-72. Pubmed: 10835333


Smooth muscle constriction in asthma causes the airway to buckle into a rosette pattern, folding the epithelium into deep crevasses. The epithelial cells in these folds are pushed up against each other and thereby experience compressive stresses. To study the epithelial cell response to compressive stress, we subjected primary cultures of rat tracheal epithelial cells to constant elevated pressures on their apical surface (i.e., a transmembrane pressure) and examined changes in the expression of genes that are important for extracellular matrix production and maintenance of smooth muscle activation. Northern blot analysis of RNA extracted from cells subjected to transmembrane pressure showed induction of early growth response-1 (Egr-1), endothelin-1, and transforming growth factor-beta1 in a pressure-dependent and time-dependent manner. Increases in Egr-1 protein were detected by immunohistochemistry. Our results demonstrate that airway epithelial cells respond rapidly to compressive stresses. Potential transduction mechanisms of transmembrane pressure were also investigated.

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Rich Lee seeks to understand heart failure and metabolic diseases that accompany human aging, and translate that understanding into therapies. Lee is an active clinician, regularly treating patients at Brigham and Women’s Hospital.

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