The ability to treat or cure a human disease depends upon the ability to perform valuable and informative basic science, clinical science, and translational studies. For the disease idiopathic pulmonary fibrosis (IPF), many researchers utilize basic science models to uncover the molecular details surrounding the development of this disease. These models are essential, but they are limited by the fact that they do not completely represent the human phenotype and function best as an artificial system. Although performing retrospective or prospective studies on humans with IPF is extremely difficult, these proof-of-concept studies must be done to confirm any details revealed from the use of basic science models. There is no known cause or cure for IPF, but the characterization of the molecular pathways associated with this disease, using both basic science models and human tissues, will certainly lead to a novel discovery, treatment, or cure for this devastating disease. The broad, long-term objectives of this grant include: 1) Provide proof-of-concept studies with human specimens;2) Obtain a better understanding of the involvement of M-CSF, CCL8, CCL2, and CCR2 in human IPF;3) Gain insight into the characteristics of fibrocytes in lung tissue sections from patients with IPF;4) Correlate the molecular and cellular characteristics with the absence, presence, and severity of disease using all available clinical data. To achieve these goals, the following three specific aims will be used: 1) Determine the expression profiles of M-CSF, CCL8, CCL2, and CCR2 in patients with IPF;2) Characterize and identify fibrocytes in lung tissue sections from patients with IPF;3) Correlate the gathered lung molecular, phenotypic data to patient clinical data using statistical models. In doing so, these studies will lend precedence to further investigation of these factors as possible therapeutic agents to combat lung fibrosis, or for the prospective use as novel biomarkers of disease, which correlates with the mission of the National Heart, Lung, and Blood Institute of the National Institutes of Health. The objectives and aims of this grant will be accomplished by using the following methods. Tissue sections will be used for immunohistochemical methods, such as basic single staining, complex dual immunohistochemistry, and in situ hybridization. Tissue sections will also be used to isolate protein and RNA for activation and expression assays, including ELISA analysis, western blotting, and Real Time PCR. Lastly, patient clinical data will be used to perform statistical correlations between the presence or severity of disease and all quantifiable data obtained from patient specimens. (End of Abstract)
Project Narrative: The goals and objectives of this grant include the use of specimens from humans with idiopathic pulmonary fibrosis in order to facilitate a better understanding of the processes that are involved in the development of the disease. This will allow for future investigation into potential therapeutic drug design and/or biomarkers of disease for a disease that has no known cause or cure.
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| Bringardner, Benjamin D; Baran, Christopher P; Eubank, Timothy D et al. (2008) The role of inflammation in the pathogenesis of idiopathic pulmonary fibrosis. Antioxid Redox Signal 10:287-301 |
