The extracellular matrix - the under-recognized element in lung disease?
The lung is composed of airways and lung parenchyma, and the extracellular matrix (ECM) contains the main building blocks of both components. The ECM provides physical support and stability to the lung, and as such it has in the past been regarded as an inert structure. More recent research has provided novel insights revealing that the ECM is also a bioactive environment that orchestrates the cellular responses in its environs. Changes in the ECM in the airway or parenchymal tissues are now recognized in the pathological profiles of many respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Only recently have we begun to investigate whether these ECM changes result from the disease process, or whether they constitute a driving factor that orchestrates the pathological outcomes. This review summarizes our current knowledge of the alterations in the ECM in asthma, COPD, and IPF, and the contributions of these alterations to the pathologies. Emerging data suggest that alterations in the composition, folding or rigidity of ECM proteins may alter the functional responses of cells within their environs, and in so doing change the pathological outcomes. These characteristics highlight potential avenues for targeting lung pathologies in the future. This may ultimately contribute to a better understanding of chronic lung diseases, and novel approaches for finding therapeutic solutions. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
University of Groningen, University Medical Centre Groningen, GRIAC Research Institute, Department of Pathology and Medical Biology, Groningen, The Netherlands.|Respiratory Cellular and Molecular Biology Group, Woolcock Institute of Medical Research, The University of Sydney, Glebe, NSW, Australia.|Discipline of Pharmacology, The University of Sydney, NSW, Australia.|Central Clinical School, The University of Sydney, NSW, Australia.
Janette K
JK
Burgess
Department of Pathology, São Paulo University Medical School, São Paulo, Brazil.
Thais
T
Mauad
Respiratory Cellular and Molecular Biology Group, Woolcock Institute of Medical Research, The University of Sydney, Glebe, NSW, Australia.|Central Clinical School, The University of Sydney, NSW, Australia.
Gavin
G
Tjin
Lung Biology, Department of Experimental Medical Sciences, Medical Faculty, Lund University, Lund, Sweden.
Jenny C
JC
Karlsson
Lung Biology, Department of Experimental Medical Sciences, Medical Faculty, Lund University, Lund, Sweden.
Gunilla
G
Westergren-Thorsson
D001249:Asthma / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000378:metabolism / Q000473:pathology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000473:pathology
D016326:Extracellular Matrix Proteins; D005938:Glucocorticoids
asthma; chronic obstructive pulmonary disease; collagen; extracellular matrix; fibrosis; lung; myofibroblast; niche