This proposal will test the hypothesis that protease-induced lung injury results in the release of cell surface heparan sulfate proteoglycans (HSPG) which participate in modulating the repair responses of pulmonary fibroblasts.
The specific aims of the proposed studies are 1) to define the role of HSPG in modulating the pulmonary fibroblast response to elastolytic injury; 2) to identify and characterize alterations in elastin synthesis and deposition following depletion of cell surface proteoglycans; and 3) to identify and characterize changes in proteoglycan composition following elastase treatment. The proposed studies will utilize a combination of pharmacological and enzymatic interventions which will generate HSPG-deficient fibroblasts which will be subject to protease treatment. Morphological and biochemical changes will be determined using microscopic and biochemical techniques. Delineation of the role of proteoglycans in elastolytic lung injury may lead to the identification of novel sites for drug intervention in patients with impaired pulmonary function due to chronic obstructive pulmonary disease.
| Buczek-Thomas, Jo Ann; Lucey, Edgar C; Stone, Phillip J et al. (2004) Elastase mediates the release of growth factors from lung in vivo. Am J Respir Cell Mol Biol 31:344-50 |
| Buczek-Thomas, Jo Ann; Chu, Chia L; Rich, Celeste B et al. (2002) Heparan sulfate depletion within pulmonary fibroblasts: implications for elastogenesis and repair. J Cell Physiol 192:294-303 |
