Research Project: Learning About Tissue Stiffness in Pulmonary Fibrosis
basic biologic mechanisms
Pulmonary fibrosis (PF) is a progressive disease in which a patient’s lungs are scarred, often for unknown reasons. Over time, the scarred tissue prevents oxygen from being taken up by the blood, leading to shortness of breath and often death. There is currently no cure for PF. Thus, there is a critical need to better understand PF and identify new therapeutic targets. Tissue stiffness due to scarring and accumulation of abnormal cells are characteristic for lungs with PF. Current cell culture systems this involve plastic, which does not mimic the environment inside the body. To address this problem, we have developed biomaterial-based culture systems to study the response of cells to different stiffnesses. Our overall focus is to understand how tissue stiffness accelerates the growth of these abnormal cells and their communication with other cells during fibrosis. We believe these insights will provide important knowledge towards targeting tissue stiffness-related changes in PF.
During the first year of this award, we focused on developing a novel approach of changing the stiffness of the existing environment of lung cells. Our results are promising and showed that these aberrant cells indeed accumulate in regions of stiffened extracellular matrix, the complex network of proteins that provides structural support for cells and tissues. This is significant since it indicates that our platform is capable of recreating this aspect of early fibrotic remodeling and that provides an in vitro culture system to study the response and behavior of these cells. In the upcoming year of this award, we will be focusing on studying the intracellular mechanisms of cellular responses and their crosstalk with other cells within the lung.