The lung's unique extracellular matrix (ECM), while providing structural support for cells, is critical in the regulation of developmental organogenesis, homeostasis and injury-repair responses. The ECM, via biochemical or biomechanical cues, regulates diverse cell functions, fate and phenotype. The composition and function of lung ECM become markedly deranged in pathological tissue remodeling. ECM-based therapeutics and bioengineering approaches represent promising novel strategies for regeneration/repair of the lung and treatment of chronic lung diseases. In this review, we assess the current state of lung ECM biology, including fundamental advances in ECM composition, dynamics, topography, and biomechanics; the role of the ECM in normal and aberrant lung development, adult lung diseases and autoimmunity; and ECM in the regulation of the stem cell niche. We identify opportunities to advance the field of lung ECM biology and provide a set recommendations for research priorities to advance knowledge that would inform novel approaches to the pathogenesis, diagnosis, and treatment of chronic lung diseases.
Bibliographical noteFunding Information:
We acknowledge the support of the Division of Lung Diseases, National Heart, Lung & Blood Institute which initially organized a workshop on this topic on September 17?18, 2014 in Bethesda, Maryland. All authors of this manuscript participated in this workshop. The authors thank J. Michael Wells, MD, Derek Russell, MD and J. Edwin Blalock, PhD for their contributions to the construction of Fig. 5.