Hypothesis: The pulmonary myofibroblast plays a central role in the development of lung fibrosis. The local environment, associated with cyclical stretch and expression of TGF-beta, favors the use of signal transduction pathways that lead to the development of cells with properties and gene expression patterns of both muscle cells and fibroblasts. The increased matrix synthesis of these cells decreases the compliance of the tissue, leading to mechanotransduction events tht further increase synthesis of matrix. Figure 1. Postulated sequence of development of progressive fibrosis in vitro, wherein only fibroblasts, matrix, TGF-beta and physical forces are allowed to operate. We hypothesize that the unique mechanical properties of the lung permits (in the presence of TGF-beta) progression of stress-sensitive fibroblasts to myofibroblasts, and increases matrix production that increases stress.
| Cha, Seung-Ick; Groshong, Steve D; Frankel, Stephen K et al. (2010) Compartmentalized expression of c-FLIP in lung tissues of patients with idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol 42:140-8 |
| Swigris, Jeffrey J; Swick, Jeff; Wamboldt, Frederick S et al. (2009) Heart rate recovery after 6-min walk test predicts survival in patients with idiopathic pulmonary fibrosis. Chest 136:841-848 |
| Kinder, Brent W; Brown, Kevin K; McCormack, Francis X et al. (2009) Serum surfactant protein-A is a strong predictor of early mortality in idiopathic pulmonary fibrosis. Chest 135:1557-1563 |
