Toward a Better Understanding of...
The Role of FGF2 Signaling in a Naphthalene Lung Injury Model Timothy Elton Mentors: Rob Guzy and David Ornitz Lung disease is the fourth leading cause of death and disability in the United States. To better understand diseases that affect the adult lung, it is necessary to study the signaling pathways that are activated in response to tissue injury. Fibroblast Growth Factors (FGFs) are a family of growth factors and receptors that are key signaling molecules for growth, development, and repair. Fibroblast Growth Factor 2 (FGF2) has been shown to be important in wound healing, myocardial infarction recovery, and implicated in the pathogenesis of pulmonary fibrosis. In previous studies, mice lacking Fgf2 (Fgf2 -/- mice) showed an increased mortality after bleomycin-induced lung injury, which models pulmonary fibrosis. We hypothesized that the main underlying phenotype of Fgf2 -/-mice is a deficiency in epithelial repair. To test this, we implemented a model in which we gave Naphthalene to Fgf2 -/-mice and compared their recovery to wild type mice. Naphthalene is a drug that causes damage to Clara cells, a specialized lung epithelial cell that expresses a secretory protein (CCSP) that can be readily detected by immunostaining. The mice were observed during a recovery period of 10-14 days. After looking at lung histology and immunostaining, we anticipate observing a delayed recovery of CCSP expressing cells and a decreased number of proliferating cells at peak injury in Fgf2 -/- mice. Based on initial examination, Fgf2 -/- mice appear to exhibit a delay in lung epithelial recovery. However, further examination and larger sample size is required for statistical significance and fully conclusive results.
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