Alveolar epithelial-to-mesenchymal transition in scleroderma interstitial lung disease: Technical challenges, available evidence and therapeutic perspectives

Abstract

The alveolar epithelial-to-mesenchymal transition is the process of transformation of differentiated epithelial cells into mesenchymal-like cells through functional and morphological changes. A partial epithelial-to-mesenchymal transition process can indirectly contribute to lung fibrosis through a paracrine stimulation of the surrounding cells, while a finalized process could also directly enhance the pool of pulmonary fibroblasts and the extracellular matrix deposition. The direct demonstration of alveolar epithelial-to-mesenchymal transition in scleroderma-related interstitial lung disease is challenging due to technical pitfalls and the limited availability of lung tissue samples. Similarly, any inference on epithelial-to-mesenchymal transition occurrence driven from preclinical models should consider the limitations of cell cultures and animal models. Notwithstanding, while the occurrence or the relevance of this phenomenon in scleroderma-related interstitial lung disease have not been directly and conclusively demonstrated until now, pre-clinical and clinical evidence supports the potential role of epithelial-to-mesenchymal transition in the development and progression of lung fibrosis. Evidence consolidation on scleroderma-related interstitial lung disease epithelial-to-mesenchymal transition would pave the way for new therapeutic opportunities to prevent, slow or even reverse lung fibrosis, drawing lessons from current research lines in neoplastic epithelial-to-mesenchymal transition.