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

  • Janette K. Burgess
  • Kirsten Muizer
  • Corry-Anke Brandsma
  • Irene H. Heijink
Chapter
Part of the Molecular and Translational Medicine book series (MOLEMED)

Abstract

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.

Keywords

Asthma Chronic obstructive pulmonary disease (COPD) Idiopathic pulmonary fibrosis (IPF) Fibrosis Extracellular matrix 

Abbreviations

ADSCs

Adipose-derived MSCs

ASM

Airway smooth muscle

ATI

Alveolar type I cells

ATII

Alveolar type II cells

BAL

Bronchoalveolar lavage

BM

Basement membrane

BM-MSCs

Bone marrow-derived MSCs

BOS

Bronchiolitis obliterans syndrome

COPD

Chronic obstructive pulmonary disease

DAMPs

Damage-associated molecular patterns

ECM

Extracellular matrix

EMT

Epithelial-to-mesenchymal transition

ER

Endoplasmic reticulum

FGF

Fibroblast growth factor

HGF

Hepatocyte growth factor

HSPG

Heparin sulfate proteoglycan

IGF

Insulin-like growth factor

IPF

Idiopathic pulmonary disease

MMPs

Matrix metalloproteinases

MSCs

Mesenchymal stromal/stem cells

PDGF

Platelet-derived growth factor

PG

Proteoglycan

PGE2

Prostaglandin E2

SFPTC

Pro-surfactant protein C

TGF

Transforming growth factor

UC-MSCs

Umbilical cord-derived MSCs

VEGF

Vascular endothelial growth factor

WNT

Wingless/integrase-1

YAP

Yes-associated protein

α-SMA

Alpha-smooth muscle actin

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Janette K. Burgess
    • 1
  • Kirsten Muizer
    • 1
  • Corry-Anke Brandsma
    • 1
  • Irene H. Heijink
    • 1
  1. 1.University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, GRIAC (Groningen Research Institute for Asthma and COPD)GroningenThe Netherlands

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