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Targeted Injury of Type II Alveolar Epithelial Cells Induces Pulmonary Fibrosis

By Thomas H. Sisson, Michael Mendez, Karen Choi, Natalya Subbotina, Anthony Courey, Andrew Cunningham, Aditi Dave, John F. Engelhardt, Xiaoming Liu, Eric S. White, Victor J. Thannickal, Bethany B. Moore, Paul J. Christensen and Richard H. Simon


Rationale: Ineffective repair of a damaged alveolar epithelium has been postulated to cause pulmonary fibrosis. In support of this theory, epithelial cell abnormalities, including hyperplasia, apoptosis, and persistent denudation of the alveolar basement membrane, are found in the lungs of humans with idiopathic pulmonary fibrosis and in animal models of fibrotic lung disease. Furthermore, mutations in genes that affect regenerative capacity or that cause injury/ apoptosis of type II alveolar epithelial cells have been identified in familial forms of pulmonary fibrosis. Although these findings are compelling, there are no studies that demonstrate a direct role for the alveolar epithelium or, more specifically, type II cells in the scarring process. Objectives: To determine if a targeted injury to type II cells would result in pulmonary fibrosis. Methods: A transgenic mouse was generated to express the huma

Year: 2014
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