The purpose of this review is to describe the contribution of an altered, profibrotic extracellular matrix (ECM) microenvironment to pulmonary fibrosis and how it changes cell behaviour and actively drives disease progression.
Idiopathic pulmonary fibrosis is a chronic and fatal disease of unknown cause. It is characterized by proliferation and accumulation of fibroblasts and myofibroblasts in clusters, termed fibroblastic foci, and extensive ECM deposition. Recent evidence from in-vivo and ex-vivo experimental studies has highlighted that the abnormal ECM in fibrotic lungs alters the behaviour of epithelial and mesenchymal cells. This profibrotic ECM microenvironment is characterized by altered biochemical and biomechanical properties and stores abundant amount of growth factors. By this, the ‘fibrotic ECM’ can drive progressive fibrogenesis in the lungs without any further initiating trigger. These concepts indicate a more complicated dynamic and active role of the fibrotic ECM than previously thought and offer many novel therapeutic targets.
The fibrotic ECM microenvironment is an active contributor to the development and progression of pulmonary fibrosis and a promising therapeutic target.
aDepartment of Medicine, McMaster University, Firestone Institute for Respiratory Health, Hamilton, Ontario, Canada
bDepartment of Pharmacology, Shimane University School of Medicine, Shimane, Japan
Correspondence to Martin Kolb, MD, PhD, Department of Medicine, Pathology and Molecular Medicine, McMaster University, Firestone Institute for Respiratory Health, 50 Charlton Ave East, Room T2131, Hamilton, ON L8N 4A6, Canada. Tel: +1 905 522 1155 x34973; fax: +1 905 521 6183; e-mail: email@example.com