Tissue remodelling in chronic bronchial diseases: from the epithelial to mesenchymal phenotype

Abstract

Airway remodelling is a critical feature of chronic bronchial diseases, characterised by aberrant repair of the epithelium and accumulation of fibroblasts, which contribute to extracellular matrix (ECM) deposition resulting in fixed bronchial obstruction. Recently, epithelial-mesenchymal transition (EMT) has been identified as a new source of fibroblasts that could contribute to the remodelling of the airways. This phenomenon consists of the loss of the epithelial phenotype by bronchial epithelial cells and the acquisition of a mesenchymal phenotype. These cells are then able to migrate and secrete ECM molecules. Herein, we review the different types of EMT. We will then focus on the signalling pathways that are involved, such as transforming growth factor-b and Wnt, as well as the more recently described Sonic Hedgehog pathway. Finally, we will highlight the implication of EMT in airway remodelling in specific chronic bronchial pathologies, such as asthma, chronic obstructive pulmonary disease and bronchiolitis obliterans following lung transplantation. Despite the limitations of in vitro models, future studies of EMT in vivo are warranted to shed new light on the pathomechanisms of bronchial obstruction. @ERSpublications Epithelial-mesenchymal transition in chronic bronchial remodelling diseases

Imprinting of the COPD airway epithelium for dedifferentiation and mesenchymal transition

“…It was also shown that EMT could be induced in vitro in (human and rat) alveolar epithelial cells, notably by TGF-β [21]. In contrast, the occurrence and relevance of EMT in chronic airway diseases remains debated [22,23]. Findings in experimental asthma and in vitro epithelial responses to TGF-β and allergens suggested a role for EMT in allergic asthma [24], but direct evidence of constitutive overexpression of mesenchymal markers by the asthmatic bronchial epithelium is lacking.…”

A novel regulatory role for tissue transglutaminase in epithelial-mesenchymal transition in cystic fibrosis

“…Interestingly EMT has also been shown to occur in chronic obstructive pulmonary disease [41], where patients have many comparable clinical symptoms to that of CF sufferers.…”

Take the Wnt out of the inflammatory sails: modulatory effects of Wnt in airway diseases

“…This transition is characterized by reduction of their cell-to-cell contacts, the downregulation of certain markers (such as E-cadherin, claudin, or mucin-1), enhanced cell migration, and induction of mesenchymal gene expression (such as Snail 1, fibronectin, α-smooth muscle actin (α-SMA), vimentin, and cyclin D1). 90,91 Different reports suggest that EMT is linked to airway remodeling in asthma. 70,92 Interestingly, EMT is regulated by the Wnt/β-catenin and the noncanonical Wnt signaling pathway.…”