Dynamic Reciprocity: The Role of the Extracellular Matrix Microenvironment in Amplifying and Sustaining Pathological Lung Fibrosis

When taken together fibrotic lung diseases are the leading cause of mortality worldwide, but our understanding of the underlying mechanisms driving these processes is limited. The lung consists of defined parts including the airways and parenchyma. The principal building blocks of these parts are the extracellular matrix (ECM). The ECM supports cells structurally while also acting as a bioactive environment directing cellular responses during pathological events in the lung. Airway and parenchymal tissue ECM alterations characterize the changes identified in many fibrotic lung diseases, including in asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Characterization of the profiles of changes and investigation into how these ECM changes contribute to the disease process has been the recent focus within the field. Studies suggest that the changes in the composition, organization, and stiffness of the ECM environment in the lung may drive functional responses of cells and thereby contribute to the pathological outcome. This chapter aims to summarize the state of the art regarding the dynamic interchange of the ECM in pulmonary fibrotic diseases and the approaches for modulating these aberrations in the future. The overarching goal is to expand knowledge of the contributions of the ECM to enable a better understanding of fibrotic lung diseases and to identify novel approaches for therapeutic targeting in this area.