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Differential Gene Expression of sFRP-1 and Apoptosis in Pulmonary Emphysema* FREE TO VIEW

Kazushi Imai, DDS, PhD; Jeanine D’Armiento, MD, PhD
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*From the Division of Molecular Medicine, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY.

Correspondence to: Jeanine D’Armiento, MD, PhD, Assistant Professor of Medicine, Columbia University, 630 W 168th St, P&S 9–449, New York, NY 10032; e-mail: jmd12@columbia.edu

Chest. 2002;121(3_suppl):7S. doi:10.1378/chest.121.3_suppl.7S
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In order to identify the unique molecular pathways that are involved in emphysema, a differential display analysis was performed on lung tissue to identify the genes expressed in the lung tissue of emphysema patients but not in that of patients with healthy lungs. We detected 142 differentially expressed genes. One of these genes, secreted frizzled-related protein sFRP-1, an inhibitor of Wnt signaling, was further characterized by its role in the pathophysiology of emphysema. Although this gene was not detected in the healthy adult mouse lung, it was expressed in the distal epithelial cells of the lung during development and also in the lung in two separate mouse emphysema models. Since the Wnt pathway is involved in proliferation and apoptosis, a study was undertaken that determined that tissue from the emphysematous lung of human patients was undergoing apoptosis. The apoptotic index closely correlated with the severity of disease. In vitro tissue transfection studies have confirmed that sFRP-1 leads to apoptosis of pulmonary epithelial and endothelial cells. The identification of sFRP-1 in emphysema has provided us with novel insight into the pathophysiology of this disease. The characterization of the other 142 differentially expressed genes will allow us to further identify the changes in gene expression in this disease. These genes have been placed on array chips so as to compare the differential gene expression from patients at various clinical stages of COPD with that of smokers prior to the development of COPD.




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