Based on clinical and experimental observations, a new paradigm has progressively emerged with the alveolar epithelium being viewed as a key actor in the development of ILD [17] [18] [19] . Following injury, alveolar epithelial cells (AEC) may actively participate in the restoration of a normal alveolar architecture through a coordinated process of re-epithelialization, or in the development of fibrosis through a process known as epithelial-mesenchymal transition (EMT) [20] . Complex networks orchestrate EMT leading to changes in cell architecture and behaviour, loss of epithelial characteristics and gain of mesenchymal properties. The reasons for epithelial cell loss and inappropriate re-epithelialisation are still debated, but ongoing apoptosis is believed to be a key component in the progression of the disorder [21] . Prolonged denudation of the basement membrane contributes to altered interactions and cross-talk between AECs and mesenchymal cells, resulting in profound modifications of cell functions with imbalanced production of oxidants, proteases, and polypeptide mediators including cytokines and growth factors such as Transforming Growth Factor (TGF)-β and Endothelin (ET)-1. A consequence is the perpetuation of a vicious cycle with TGF-β promoting epithelial cell apoptosis, which in turn increases the local production of TGF-β [22] . ET-1 is also considered to be an important actor, based on the current knowledge of its numerous functions including fibroblast and smooth muscle cell mitogen, and stimulant of collagen synthesis [23, 24] . Recent studies showed that ET-1 is produced by AEC, and could induce alveolar EMT via stimulation of endogenous TGF-β production.