Epithelial–mesenchymal transition in the pathophysiology of airway remodelling in asthma

We currently understand little about the mechanisms that lead to airway remodeling in asthma. The origin of the mesenchymal cells that contribute to fibrosis of the airway is poorly understood. However, emerging evidence suggests that the airway epithelium could contribute to airway remodeling through the process of epithelial-mesenchymal transition (EMT) following environmental challenge. In this review, we will discuss the mechanistic features of EMT and highlight recent descriptions of EMT in the airway to further define the role of the airway epithelium in the pathogenesis of asthma.Growth factors, inflammatory mediators, and matricellular proteins expressed following exposure to environmental insults are known to induce downregulation of epithelial cell-cell adhesions and promote mesenchymal gene expression programs both in vitro and in vivo. These results demonstrate that the plastic and dynamic airway epithelium may contribute to airway remodeling via EMT in asthma.It is becoming increasingly clear that the airway epithelium orchestrates inflammatory and remodeling responses of the airway. Understanding the regulatory mechanisms involved in epithelial plasticity will be crucial to determine effective therapies to halt the progression of airway remodeling in asthma.