STAT3 AND SMAD SIGNALING IN MOUSE MODELS OF ONCOSTATIN M- INDUCED LUNG EXTRACELLULAR MATRIX REMODELING

iii IPF is a respiratory condition of unknown etiology that has poor survival prognosis. The stiffening of the lung associated with this condition is attributed to the irreversible turnover of healthy lung tissue into scar tissue, which affects gas exchange and can eventually lead to organ failure. Numerous studies have implicated the pro-fibrogenic growth factor TGF-β, through activation of the SMAD2/3 pathway, as a central mediator in the pathology of this condition. However, other cytokines, including members of the IL-6/gp130 family such as OSM, and other signaling pathways may be implicated in ECM accumulation in certain conditions. In particular, STAT3 activation and an impairment of the BMP-SMAD1 signaling axis is thought to contribute to lung ECM accumulation. Based on the finding that transient pulmonary overexpression of OSM induces lung ECM accumulation in C57Bl/6 mice, it was hypothesized that OSM-induced ECM remodeling would be associated with STAT3 activation and suppression of the BMP-SMAD1-signaling axis