The extracellular matrix – the under‐recognized element in lung disease?

Abstract

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.

Interplay of extracellular matrix and leukocytes in lung inflammation

“…For the purpose of this review, we will focus on versican and hyaluronan, two interstitial ECM components [3] that can serve as ligands for leukocytes and impact immune and inflammatory responses in lung disease [3–7]. In addition, we will discuss how specific leukocytes, such as the macrophage, interact with the ECM and the importance of a specific matrix metalloproteinase (MMP), MMP10, in controlling the state of macrophage activation in lung disease.…”

Fibrillin-2 and Tenascin-C bridge the age gap in lung epithelial regeneration

“…When considering the ECM in whole organ regeneration, the source of native lung tissue used to prepare the scaffold can have a direct impact on subsequent regeneration. Several studies have shown that underlying lung pathologies can cause changes in the ECM that are retained following decellularization, and can perpetuate during tissue repair (5). This has been demonstrated for both pulmonary fibrosis and emphysema (6, 7).…”

VEGF synthesis is induced by prostacyclin and TGF‐β in distal lung fibroblasts from COPD patients and control subjects: Implications for pulmonary vascular remodelling

“…VEGF is synthesized by epithelial cells, smooth muscle cells, mast cells, alveolar macrophages and fibroblasts . Fibroblasts are key regulators of extracellular matrix (ECM) proteins and constitute a rich source of growth factors . Interestingly, the vascular mediator prostacyclin may induce VEGF and prostacyclin is synthesized in high amounts by distal lung fibroblasts from severe COPD patients .…”

“…15,16 Fibroblasts are key regulators of extracellular matrix (ECM) proteins and constitute a rich source of growth factors. 1,17 Interestingly, the vascular mediator prostacyclin may induce VEGF 15 and prostacyclin is synthesized in high amounts by distal lung fibroblasts from severe COPD patients. 18 Our recent data imply that severe COPD patients may have altered fibroblast function and defective repair mechanisms in the ECM structure in response to prostacyclin.…”