DESCRIPTION (provided by applicant): Idiopathic Pulmonary Fibrosis (IPF) is a deadly interstitial lung disease. Short of lung transplantation there is no proven effective treatment for the disease process. The disease is characterized by progressive scarring of the airspaces. The primary cell type responsible for the progressive scarring is the lung fibroblast. Recent work suggests that the lung fibroblast in IPF has distinct pathological properties enabling it to abnormally proliferate and survive. However, large gaps in knowledge remain regarding differences between the pathological nature of fibroblasts in IPF responsible for progressive proliferation and the limited physiological proliferation of normal fibroblasts necessary for prope lung repair. In preliminary studies, we have discovered pathological alterations in key signaling pathways that regulate IPF fibroblast proliferation and survival. This proposal seeks to further characterize key differences between normal and IPF fibroblasts that underline the aberrant ability of IPF fibroblasts to proliferate and scar airspaces. These experiments could suggest new therapeutic strategies for this lethal disease.

PUBLIC HEALTH RELEVANCE: Idiopathic Pulmonary Fibrosis (IPF) is a lethal lung disease and currently there is no effective medical therapy available to cure or prevent this disease. In this study, we have found that crucial signaling molecules are abnormally altered in IPF fibroblasts and in lung specimens with IPF. Thus the elucidation of pathological mechanisms in IPF fibroblasts greatly helps design a therapeutic target to limit the progression of IPF.