TY - JOUR
T1 - Airway epithelial barrier dysfunction in chronic obstructive pulmonary disease
T2 - Role of cigarette smoke exposure
AU - Aghapour, Mahyar
AU - Raee, Pourya
AU - Moghaddam, Seyed Javad
AU - Hiemstra, Pieter S.
AU - Heijink, Irene H.
N1 - Publisher Copyright:
Copyright © 2018 by the American Thoracic Society
PY - 2018/2
Y1 - 2018/2
N2 - The epithelial lining of the airway forms the first barrier against environmental insults, such as inhaled cigarette smoke, which is the primary risk factor for the development of chronic obstructive pulmonary disease (COPD). The barrier is formed by airway epithelial junctions, which are interconnected structures that restrict permeability to inhaled pathogens and environmental stressors. Destruction of the epithelial barrier not only exposes subepithelial layers to hazardous agents in the inspired air, but also alters the normal function of epithelial cells, which may eventually contribute to the development of COPD. Of note, disruption of epithelial junctions may lead to modulation of signaling pathways involved in differentiation, repair, and proinflammatory responses. Epithelial barrier dysfunction may be particularly relevant in COPD, where repeated injury by cigarette smoke exposure, pathogens, inflammatory mediators, and impaired epithelial regeneration may compromise the barrier function. In the current review, we discuss recent advances in understanding the mechanisms of barrier dysfunction in COPD, as well as the molecular mechanisms that underlie the impaired repair response of the injured epithelium in COPD and its inability to redifferentiate into a functionally intact epithelium.
AB - The epithelial lining of the airway forms the first barrier against environmental insults, such as inhaled cigarette smoke, which is the primary risk factor for the development of chronic obstructive pulmonary disease (COPD). The barrier is formed by airway epithelial junctions, which are interconnected structures that restrict permeability to inhaled pathogens and environmental stressors. Destruction of the epithelial barrier not only exposes subepithelial layers to hazardous agents in the inspired air, but also alters the normal function of epithelial cells, which may eventually contribute to the development of COPD. Of note, disruption of epithelial junctions may lead to modulation of signaling pathways involved in differentiation, repair, and proinflammatory responses. Epithelial barrier dysfunction may be particularly relevant in COPD, where repeated injury by cigarette smoke exposure, pathogens, inflammatory mediators, and impaired epithelial regeneration may compromise the barrier function. In the current review, we discuss recent advances in understanding the mechanisms of barrier dysfunction in COPD, as well as the molecular mechanisms that underlie the impaired repair response of the injured epithelium in COPD and its inability to redifferentiate into a functionally intact epithelium.
KW - COPD
KW - Cigarette smoke
KW - Epithelial barrier function
KW - Epithelial junctions
UR - http://www.scopus.com/inward/record.url?scp=85043350858&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85043350858&partnerID=8YFLogxK
U2 - 10.1165/rcmb.2017-0200TR
DO - 10.1165/rcmb.2017-0200TR
M3 - Editorial
C2 - 28933915
AN - SCOPUS:85043350858
SN - 1044-1549
VL - 58
SP - 157
EP - 169
JO - American journal of respiratory cell and molecular biology
JF - American journal of respiratory cell and molecular biology
IS - 2
ER -